pH/温度敏感的水凝胶粒子/微球的制备、表征及其在药物缓释中的应用
|
摘要
本论文以羧甲基壳聚糖(CMCTS)和甲基丙烯酸(MAA)为pH敏感的功能性单体,以N,N-二乙基丙烯酰胺(DEA)为温度敏感的功能性单体,采用不同的实验方法,制备了具有不同尺寸的球形结构的凝胶；通过改变聚合物的结构及组成,调整载药凝胶在不同生理环境下的释药速率；通过对凝胶生物相容性的初步研究,显示出其在临床口服药物载体方面特别是肠部定位释药方面具有良好的应用前景。取得的主要结果有：
1.采用自由基溶液聚合的方法,合成了一系列可溶于碱性溶液的羧甲基壳聚糖-graft-聚N-乙烯基吡咯烷酮(CMCTS-g-PVP)聚合物,采用离子交联的方法得到了所需的凝胶粒子；溶胀实验表明,该凝胶粒子具有明显的pH敏感性；对VB2药物的释放结果表明,凝胶粒子在pH=1.2的缓冲溶液中的药物释放速率明显低于在pH=7.4时的药物释放速率：通过增加交联剂浓度及CMCTS-g-PVP的接枝率,可以明显降低载药粒子的释药速率。
2.在上述工作的基础上,合成了一系列具有不同接枝率的羧甲基壳聚糖-graft-聚N,N-二乙基丙烯酰胺(CMCTS-g-PDEA)聚合物,将其在HCl和CaCl2的混合溶液中进行交联,得到了具有双交联键结构的凝胶粒子；溶胀实验表明,水凝胶粒子具有明显的pH值敏感性和温度敏感性,并且由于其双交联结构和较高的接枝率,该凝胶粒子在pH=7.4的介质中相对较为稳定；对比单纯用钙离子交联的凝胶粒子和含有双交联键结构的凝胶粒子的体外药物释放行为,表明具有双交联网络结构的载药粒子其缓释效果明显优于单交联的载药粒子；升高温度及增加CMCTS-g-PDEA接枝物的接枝率,均可明显降低载药粒子的释药速率。
3.采用无皂乳液聚合的方法,在水溶液中制备了具有核壳结构的P(DEA-co-MAA)凝胶微球；TEM照片显示该凝胶粒子具有明显的核壳结构；提高溶液的pH值,P(DEA-co-MAA)微凝胶在不同pH环境中流体力学直径(Dv)明显增加,并且随着MAA用量的增加,粒子直径逐渐增大；随着微球体系中MAA用量的增加,凝胶微球体积相变温度(LCST)逐渐升高,并且可接近人体的生理温度；药物释放结果表明,P(DEA-co-MAA)微球比PDEA微球具有更好的缓释效果,并且该药物运输体系可以减少牛血清蛋白(BSA)在胃液中的释放量,具有在肠部定位释放的应用前景；细胞毒性实验结果证明,P(DEA-co-MAA)具有良好的生物相容性,有望应用于生物医药领域。
4.采用简单方法制备的自组装CMCTS-g-PDEA微凝胶,通过接枝率的变化可以得到微囊和微粒两种形态,微凝胶尺寸较小；在不同pH值下药物释放结果显示,微凝胶在酸性环境中的释药速率明显低于碱性环境中的释药速率,同时微凝胶的结构对药物释放速率有很大影响,对于具有囊泡结构的微凝胶,其药物释放速率随接枝率的增大而减缓,而对于颗粒形状的微凝胶虽具有较高接枝率,但由于其网络交联密度的影响,药物释放速率较快；细胞毒性实验研究结果证明了该药物运输体系无毒、具有良好的生物相容性,并且对于细胞的增殖有一定的促进作用,具有应用于生物医药学领域的良好前景。
5.采用原子转移自由基聚合技术,制备了PHEMA-b-PDEA-b-PHEMA三嵌段聚合物,该聚合物胶束在水溶液中可自组装形成粒径均一的纳米胶束,并且聚合物胶束的临界胶束浓度较低；载药胶束的体外释药动力学研究表明载药胶束的释药过程具有明显的温度响应性,此种药物运输体系对于注射型药物的定位释放具有一定的应用前景。
In this thesis, carboxymethyl chitosan and methacrylic acid are used as pH-sensitive functional monomers, and N,N-diethylacrylamide is used as temperature-sensitive functional monomer. Thermo-and pH-sensitive hydrogel beads/microgels with different sizes and spherical structure have been synthesized by using different preparation methods to adjust the polymer composition. The drug release experiment results show that these drug carriers have good pH-and temperature-sensitivity. They could be used as suitable candidate for drug site-specific carrier in intestine, which have no cytotoxicity. The results are summarized as following:
1. A series of novel carboxymethyl chitosan grafted poly(N-vinylpyrrolidone) copolymers with different grafting percentages is synthesized. The hydrogel beads are prepared by an ionic crosslinked method. The swelling ratio experiment of the hydrogels shows that the hydrogel beads have good pH-sensitivity. From drug release experiments for these beads, it can be seen that the drug release rate decreased with increasing grafting percentage, crosslinker concentration and pH value. The preliminary results for releasing experiments of model drug show that CMCTS-g-PVP beads have better control ability than CMCTS beads. This system has a great application potentiality for the carrier and controlled-release in intestine.
2. pH-and temperature-sensitive carboxymethyl chitosan-graft poly(N,N-diethylacrylamide) (CMCTS-g-PDEA) copolymers are obtained by using free radical copolymerization in water solution. The hydrogel beads are prepared based on Ca2+ ionic crosslinking in acidic solution, and the dual crosslinked network structure is formed. The result about swelling characteristics of hydrogel beads indicates that the beads have obvious pH-and temperature-sensitivity. In vitro release results of drug-loaded beads indicate that the dual crosslinked method can effectively control the drug release rate under gastrointestinal tract conditions which is superior to traditional single crosslinked beads. In addition, increasing the grafting percentage and temperature can decrease the release rate of VB2. The dual crosslinked hydrogel beads based on carboxymethyl chitosan-graft-poly(N,N-diethylacrylamide) can serve as suitable candidate for drug site-specific carrier in intestine.
3. Temperature-and pH-responsive P(DEA-co-MAA) microspheres of nanometer size with core-shell structure have been prepared by surfactant-free emulsion polymerisation (SFEP) method. With the pH value increasing, the hydrodynamic diameter size (Dv) of the microgels significantly could increas. By increasing MAA content in the copolymers, their LCST increased, and the LCST can reach the body's physiological temperature. The in vitro release studies show that the drug release behavior of P(DEA-co-MAA) microspheres is better than the drug release behavior of PDEA microspheres. These P(DEA-co-MAA) microspheres can decrease release rate of BSA drug in gastric and accomplish purpose in controlled release for drug side-specific in intestine. The cytotoxicity of all prepared microgels is low, and they have no apparent cytotoxicity.
4. Nanosized self-assembly of CMCTS-g-PDEA microgels is obtained by simple strategy. Morphology of the self-assemby microgel can be controlled by adjusting the grafting percentage, that is, microcapsules and microparticles. The in vitro release studies show that the drug release rate of microgel in the acidic environment is significantly lower than the release rate in alkaline environment, and for the microcapsules, release percentage decreases with increasing grafting percentage. Moreover, although the microparticles have a higher grafting percentage, the drug release rate of microparticles is faster than the microcapsules because of its smaller network crosslinking density. The qualitative cytotoxicity test of the microgels shows that they have no apparent cytotoxicity.
5. The PHEMA-b-PDEA-b-PHEMA triblok copolymer is successfully synthesized by atom transfer radical polymerization method, and the copolymer can self-assemble into nanomicelles with uniform diameter in water solution. The micelles are thermodynamically stable in aqueous media with a low critical micelle concentration value. In vitro drug release from the drug-loaded micelles have a dramatically thermosensibility. To be used as drug carriers, they will accumulate at target sites and release drugs in a local hyperthemia method. The cytotoxicity of all prepared microgels is low, and they have no apparent cytotoxicity.
1.采用自由基溶液聚合的方法,合成了一系列可溶于碱性溶液的羧甲基壳聚糖-graft-聚N-乙烯基吡咯烷酮(CMCTS-g-PVP)聚合物,采用离子交联的方法得到了所需的凝胶粒子；溶胀实验表明,该凝胶粒子具有明显的pH敏感性；对VB2药物的释放结果表明,凝胶粒子在pH=1.2的缓冲溶液中的药物释放速率明显低于在pH=7.4时的药物释放速率：通过增加交联剂浓度及CMCTS-g-PVP的接枝率,可以明显降低载药粒子的释药速率。
2.在上述工作的基础上,合成了一系列具有不同接枝率的羧甲基壳聚糖-graft-聚N,N-二乙基丙烯酰胺(CMCTS-g-PDEA)聚合物,将其在HCl和CaCl2的混合溶液中进行交联,得到了具有双交联键结构的凝胶粒子；溶胀实验表明,水凝胶粒子具有明显的pH值敏感性和温度敏感性,并且由于其双交联结构和较高的接枝率,该凝胶粒子在pH=7.4的介质中相对较为稳定；对比单纯用钙离子交联的凝胶粒子和含有双交联键结构的凝胶粒子的体外药物释放行为,表明具有双交联网络结构的载药粒子其缓释效果明显优于单交联的载药粒子；升高温度及增加CMCTS-g-PDEA接枝物的接枝率,均可明显降低载药粒子的释药速率。
3.采用无皂乳液聚合的方法,在水溶液中制备了具有核壳结构的P(DEA-co-MAA)凝胶微球；TEM照片显示该凝胶粒子具有明显的核壳结构；提高溶液的pH值,P(DEA-co-MAA)微凝胶在不同pH环境中流体力学直径(Dv)明显增加,并且随着MAA用量的增加,粒子直径逐渐增大；随着微球体系中MAA用量的增加,凝胶微球体积相变温度(LCST)逐渐升高,并且可接近人体的生理温度；药物释放结果表明,P(DEA-co-MAA)微球比PDEA微球具有更好的缓释效果,并且该药物运输体系可以减少牛血清蛋白(BSA)在胃液中的释放量,具有在肠部定位释放的应用前景；细胞毒性实验结果证明,P(DEA-co-MAA)具有良好的生物相容性,有望应用于生物医药领域。
4.采用简单方法制备的自组装CMCTS-g-PDEA微凝胶,通过接枝率的变化可以得到微囊和微粒两种形态,微凝胶尺寸较小；在不同pH值下药物释放结果显示,微凝胶在酸性环境中的释药速率明显低于碱性环境中的释药速率,同时微凝胶的结构对药物释放速率有很大影响,对于具有囊泡结构的微凝胶,其药物释放速率随接枝率的增大而减缓,而对于颗粒形状的微凝胶虽具有较高接枝率,但由于其网络交联密度的影响,药物释放速率较快；细胞毒性实验研究结果证明了该药物运输体系无毒、具有良好的生物相容性,并且对于细胞的增殖有一定的促进作用,具有应用于生物医药学领域的良好前景。
5.采用原子转移自由基聚合技术,制备了PHEMA-b-PDEA-b-PHEMA三嵌段聚合物,该聚合物胶束在水溶液中可自组装形成粒径均一的纳米胶束,并且聚合物胶束的临界胶束浓度较低；载药胶束的体外释药动力学研究表明载药胶束的释药过程具有明显的温度响应性,此种药物运输体系对于注射型药物的定位释放具有一定的应用前景。
In this thesis, carboxymethyl chitosan and methacrylic acid are used as pH-sensitive functional monomers, and N,N-diethylacrylamide is used as temperature-sensitive functional monomer. Thermo-and pH-sensitive hydrogel beads/microgels with different sizes and spherical structure have been synthesized by using different preparation methods to adjust the polymer composition. The drug release experiment results show that these drug carriers have good pH-and temperature-sensitivity. They could be used as suitable candidate for drug site-specific carrier in intestine, which have no cytotoxicity. The results are summarized as following:
1. A series of novel carboxymethyl chitosan grafted poly(N-vinylpyrrolidone) copolymers with different grafting percentages is synthesized. The hydrogel beads are prepared by an ionic crosslinked method. The swelling ratio experiment of the hydrogels shows that the hydrogel beads have good pH-sensitivity. From drug release experiments for these beads, it can be seen that the drug release rate decreased with increasing grafting percentage, crosslinker concentration and pH value. The preliminary results for releasing experiments of model drug show that CMCTS-g-PVP beads have better control ability than CMCTS beads. This system has a great application potentiality for the carrier and controlled-release in intestine.
2. pH-and temperature-sensitive carboxymethyl chitosan-graft poly(N,N-diethylacrylamide) (CMCTS-g-PDEA) copolymers are obtained by using free radical copolymerization in water solution. The hydrogel beads are prepared based on Ca2+ ionic crosslinking in acidic solution, and the dual crosslinked network structure is formed. The result about swelling characteristics of hydrogel beads indicates that the beads have obvious pH-and temperature-sensitivity. In vitro release results of drug-loaded beads indicate that the dual crosslinked method can effectively control the drug release rate under gastrointestinal tract conditions which is superior to traditional single crosslinked beads. In addition, increasing the grafting percentage and temperature can decrease the release rate of VB2. The dual crosslinked hydrogel beads based on carboxymethyl chitosan-graft-poly(N,N-diethylacrylamide) can serve as suitable candidate for drug site-specific carrier in intestine.
3. Temperature-and pH-responsive P(DEA-co-MAA) microspheres of nanometer size with core-shell structure have been prepared by surfactant-free emulsion polymerisation (SFEP) method. With the pH value increasing, the hydrodynamic diameter size (Dv) of the microgels significantly could increas. By increasing MAA content in the copolymers, their LCST increased, and the LCST can reach the body's physiological temperature. The in vitro release studies show that the drug release behavior of P(DEA-co-MAA) microspheres is better than the drug release behavior of PDEA microspheres. These P(DEA-co-MAA) microspheres can decrease release rate of BSA drug in gastric and accomplish purpose in controlled release for drug side-specific in intestine. The cytotoxicity of all prepared microgels is low, and they have no apparent cytotoxicity.
4. Nanosized self-assembly of CMCTS-g-PDEA microgels is obtained by simple strategy. Morphology of the self-assemby microgel can be controlled by adjusting the grafting percentage, that is, microcapsules and microparticles. The in vitro release studies show that the drug release rate of microgel in the acidic environment is significantly lower than the release rate in alkaline environment, and for the microcapsules, release percentage decreases with increasing grafting percentage. Moreover, although the microparticles have a higher grafting percentage, the drug release rate of microparticles is faster than the microcapsules because of its smaller network crosslinking density. The qualitative cytotoxicity test of the microgels shows that they have no apparent cytotoxicity.
5. The PHEMA-b-PDEA-b-PHEMA triblok copolymer is successfully synthesized by atom transfer radical polymerization method, and the copolymer can self-assemble into nanomicelles with uniform diameter in water solution. The micelles are thermodynamically stable in aqueous media with a low critical micelle concentration value. In vitro drug release from the drug-loaded micelles have a dramatically thermosensibility. To be used as drug carriers, they will accumulate at target sites and release drugs in a local hyperthemia method. The cytotoxicity of all prepared microgels is low, and they have no apparent cytotoxicity.
引文
1. Saltzman W.M.. Drug delivery:engineering principles for drug therapy. New York:Oxford university press,2001.
2. Chess R.. Economic aspects of drug delivery. Pharm. Res.1998; 15:172-174.
3.姚康德,成国祥.智能材料.北京：化学工业出版社2002.
4.陈莉,主编.智能高分子材料.北京：化学工业出版社2005.
5. Fuji-Keizai. Market advanced drug delivery systems probing the route to growth. New York:Fuji-Keizai USA Inc,2005.
6.陆彬,药物新剂型与新技术.北京：人民卫生出版社2002.
7. Liu L.X., Khang G., Rhee J.M.. Monolithic osmotic tablet system for nifedipine delivery. J. Control. Release.2000; 67:309-322.
8. Lamprecht A., Yamamoto H., Takeuchi H.. Microsphere design for the colonic delivery of 5-fluorouracil.J. Control. Rel.2003; 90:313-322.
9. Okada H., Heya T., Igari Y.. One-month release injectable microspheres of leuprolide acetate inhibit steroidogenesis and genital organ growth in rats. Int. J. Pharm.1989; 54:231-239.
10. Santus G., Baker R.W. Osmotic drug delivery:a review of the patent literature. J.Control. Rel.1995; 35:1-21.
11. Theeuwes F.. Elementary Osmotic Pump. J. Pharm. Sci.1975; 64:1987-1991.
12. Langer R.. New methods of drug delivery. Science 1990; 249:1527-1533.
13. Langer R.. Transdermal drug delivery:past progress, current status, and future prospects. Adv. Drug. Deliver. Rev.2004; 56:557-558.
14. Riviere J.E., Papich M.G.. Potential and problems of developing transdermal patchesfor veterinary applications. Adv. Drug. Deliver. Rev.2001; 50:175-203.
15. Sakr F.M.. A programmable drug delivery system for oral administration. Int. J. Pharm.1999; 184:131-139.
16. Moriyama K., Yui N.. Regulated insulin release from bio-degradable hydrogels containing poly(ethylene glycol). J. Control. Release 1996; 42:237-248.
17. Shoji S., Esashi M.. Microflow devices and systems. J. Micromech. Microeng. 1994; 4:157-171.
18. Yih T.C, Wei C., Hammad B.. Modeling and characterization of a nanoliter drug-delivery MEMS micropump with circular bossed membrane. Nanomedicine 2005;1:164-175.
19. Santini J.T.J., Cima M.J., Langer R.. A controlled release microchip. Nature 1999; 397:335-338.
20.吴芳,张志荣.定时脉冲释药系统.药学进展2001；25：279-283.
21. Scherer. DDS develops "alarm clock" dose formulation. Pharm. J.1991; 24: 138-141.
22.候连兵.常用药物新剂型及临床应用.北京：人民军医出版社1998.
23. Weidner J.. System for time and/or site-specific oral drug delivery. Drug Discov. Today 2001; 6:1028-1029.
24. Gutierrez-Sanchez P.E., Hernandez-Leon A., Villafuerte-Robles L.. Effect of sodium bicarbonate on the properties of metronidazole floating matrix tablets. Drug Dev. Ind. Pharm.2008; 34:171-180.
25. Whitehead L.F., Collett J.H., Sharma H.L.. Floating drug delivery systems:an approach to oral controlled drug delivery via gastric retention. J. Control. Release 2000; 55:3-12.
26 Yang L., Chu J.S., Fix J.A.. Colon-specific drug delivery:new approaches and in vitro/in vivo evaluation. Int. J. Pharm.2002; 235:1-15.
27 Weyenberg W., Bozdag S., Foreman P.. Characterization and in vivo evaluation of ocular minitablets prepared with different bioadhesive Carbopol-starch components. Eur. J. Pharm. Biopharm.2006; 62:202-209.
28. Hoogstraate J.A.J., Wertz P.W.. Drug delivery via the buccal mucosa. Pharm. Sci. Technol. Today,1998; 1:309-316.
29. Ugwoke M.I, Agu R.U, Verbeke N.. Nasal mucoadhesive drug delivery: Background, applications, trends and future perspectives. Adv. Drug Del. Rev. 2005; 57:1640-1665.
30. King A.E, Morgan K., Sallenave J.M.. Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone. Biochem. Bioph. Res. Co. 2003; 310:594-599.
31. Bij P., Eyk A. D.. Comparative in vitro permeability of human vaginal, small intestinal and colonic mucosa. Int. J. Pharm.2003,261:147-152.
32. Wu P., Grainger D.W.. Drug/device combinations for local drug therapies and infection prophylaxis. Biomaterials 2006; 27:2450-2467.
33. Wang P.P., Frazier J., Brem H.. Local drug delivery to the brain. Adv. Drug Deliver. Rev.2002; 54:987-1013.
34. Williams J.A., Yuan X., Dillehay L.E.. Synthetic, implantable polymers for local delivery of IUdR to experimental human malignant glioma. Int. J. Radiation Oncology Biol. Phys.1998; 42:631-639.
35. Sershen S., West J.. Implantable, polymeric systems for modulated drug delivery. Adv. Drug. Deliver. Rev.2002; 54:1225-1235.
36. Langer R.. Drug delivery and targeting. Nature 1998; 392:5-10.
37. Torchilin V.P.. Drug targeting. Euro. J. Pharm. Sci.2000; 11:81-91.
38. Allen T., Moase E.H.. Therapeutic opportunities for targeted liposomal drug delivery. Adv. Drug. Deliver. Rev.1996; 21:117-133.
39. Zimmer A., Kreuter J.. Microspheres and nanoparticles used in ocular delivery systems. Adv. Drug Deliv. Rev.1995; 16:61-73.
40. Amadottir S.G., Kristmundsdottir T.. Increased dissolution rate by microencapsulation. Euro. J. Pharm. Sci.1996; 134-134.
41.朱盛山.药物新剂型.北京：化学工业出版社2003.
42. Okuhata Y.. Delivery of diagnostic agents for magnetic resonance imaging. Adv. Drug Deliv. Rev.1999; 37:121-137.
43. Zeng H., Sun S.H.. Syntheses, properties and potential applications of multicomponent magnetic nanoparticles. Adv. Funct. Mat.2008; 18:391-400.
44. Ho K.M., Li P.. Design and synthesis of novel magnetic core-shell polymeric particles. Langmuir 2008; 24:1801-1807.
45. Voltairas P;A, Fotiadis D.I, Michalis L.K.. Hydrodynamics of magnetic drug targeting. J. Biomech.2002; 35:813-821.
46. Pankhurst Q.A., Connolly J., Jones S. K.. Applications of magnetic nanoparticles in biomedicine.J. Phys. D:Appl. Phys.2003; 36:167-181.
47. Freiberg S., Zhu X.. Polymer microspheres for controlled drug release. Int. J. Pharm.2004; 282:1-18.
48. Soppirnath K.S, Aminabhavi T.M.. Water transport and drug release study from cross-linked polyacrylamide grafted guar gum hydrogel microspheres for the controlled release application. Eur. J. Pharm. Biopharm.2002; 53:87-98.
49. Soppimath K.S., Kulkarni A.R., Aminabhavi T.M.. Chemically modified polyacrylamide-g-guar gum-based crosslinked anionic microgels as pH-sensitive drug delivery systems:preparation and characterization. J. Control. Rel.2001; 75: 331-345.
50. Kurkuri M.D., Aminabhavi T.M.. Poly(vinyl alcohol) and poly(acrylic acid) sequential interpenetrating network pH-sensitive microspheres for the delivery of diclofenac sodium to the intestine. J. Control. Rel.2004; 96:9-20.
51. Wang C.H., Wang C.H., Hsiue G.H.. Polymeric micelles with a pH-responsive structure as intracellular drug carriers. J. Control. Rel.2005; 108:140-149.
52. Gillies E.R., Frechet J.M.J.. Dendrimers and dendritic polymers in drug delivery. Drug Discov. Today 2005; 10:35-43.
53. Majoros I.J, Thomas T.P, Mehta C.B.. Poly(amidoamine) Dendrimer-based multifunctional engineered nanodevice for cancer therapy. J. Med.Chem.2005; 48:5892-5899.
54. Thomas T.P., Patri A.K., Myc A.. In vitro targeting of synthesized antibody-conjugated dendrimer nanoparticles. Biomacromolecules 2004; 5: 2269-2274.
55. Low P.S., Antony A.C.. Folate receptor-targeted drugs for cancer and inflammatory diseases. Adv. Drug Deliv. Rev.2004; 56:1055-1058.
56. Thomas T.P, Majoros I.J, Kotlyar A.. Targeting and inhibition of cell growth by an engineered dendritic nanodevice. J. Med. Chem.2005; 48:3729-3735.
57. Galaev I.Y., Mattiasson B..'Smart'polymers and what they could do inbiotechnology and medicine. Trends Biotechnol.1999; 17:335-340.
58. Hoffman A.S., Stayton P.S., Bulmus V.. Really smart bioconjugatesof smart polymers and receptor proteins. J. Biomed. Mater. Res. A 2000; 52:577-586.
59. Gupta P., Vermani K., Garg S.. Hydrogels:from controlled release to pH-responsive drug delivery. Drug Discov. Today 2002; 7:569-579.
60. Kikuchi A., Okano T.. Intelligent thermoresponsive polymeric stationaryphases for aqueous chromatography of biological compounds. Prog. Polym. Sci.2002; 27: 1165-1193.
61.李小军,毕维笳,张国亮,张凤宝.刺激响应型药物释放体系的研究进展.现代化工 2006；7：57-61.
62. Torres-Lugo M., Garcia M., Record R.. pH-Sensitive hydrogels asgastrointestinal tract absorption enhancers:transport mechanisms ofsalmon calcitonin and other model molecules using the cell model. Biotechnol. Prog.2002; 18:612-616.
63. Torres-Lugo M., Garcia M., Record R.. Physicochemical behaviorand cytotoxic effects of p(methacrylic acid-g-ethylene glycol)nanospheres for oral delivery of proteins. J. Control. Release 2002; 80:197-205.
64. Singh D.K, Ray A.R. Biomedical applications of chitin, chitosan, andtheir derivatives. Rev. Macromol. Chem. Phys.2000; C40:69-83.
65. Chen S.L., Liu M.Z., Jin S.P., Wang B.. Preparation of ionic-crosslinked chitosan-based gel beads and effect of reaction conditions on drug release behaviors. Inter. J. Pharm.2008; 349:180-187.
66. Na K.,Seong L.E., Bae Y.H.. Adriamycin loaded pullulan acetate/sulfonamide conjugate nanoparticles responding to tumor pH:pH-dependentcell interaction, internalization and cytotoxicity in vitro. J. Control. Release 2003; 87:3-13.
67. Gaucher G., Fournier E., Le G.. Delivery of hydrophobic drugsthrough self-assembling nanostructures. In:Nano and Smart Systems. Toronto:University of Montreal,2004.
68. Liu L., Jin P., Zhang G.L..5-Fluorouracil loaded self-assembled and pH-sensitive nanoparticles as a novel drug carrier for treatment of malignant tumors. Chinese J. Chem. Eng.2006; 2:14-20.
69. Lee E.S., Na K., Bae Y.H.. Polymeric micelle for tumor pH and folate mediated targeting.J. Control. Release 2003; 91:103-113.
70. Lee E.S., Na K., Bae Y.H.. Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF27 tumor. J. Control. Release 2005; 103:405-418.
71. Beltran S., Hooper H.H., Blanch H.W.. Swelling equilibria for ionized temperature-sensitive gels in water and in aqueous saltsolutions.J. Chem. Phys. 1990; 92:2061-2066.
72. Chung J.E., Yokoyama M., Yamato M.. Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isop ropylacrylamide) and poly (butylmethac-rylate).J. Control. Release 1999; 62: 115-127.
73. Lyubarsky A.L., Savchenko A.B., Morocco S.B.. Mole quantity of RPE65 and its productivity in the generation of cisretinal from retinyl esters in the living mouse eye. Biochem istry 2005; 44:9880-9888.
74. Liu X.M., Yang B., Wang Y.L.. New nanoscale pulsatile drug delivery system. Chem. Mater.2005; 17:2792-2795.
75. Chung J.E.,Yokoyama M., Yamato M.. Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly (butyl methacrylate). J. Control. Release 1999; 62:115-127.
76. Sershen S.R.,Westcott S.L.,Halas N.J.. Temperature-sensitive poly(mernanoshell composites for photothermally modulated drug delivery. J. Biomed Mater.Res. 2000; 51:293-298.
77. Jeong B.,Choi Y.K., Bae Y.H.. New biodegradable polymers for injectable drug delivery systems. J. Control. Release 1999; 62:109-114.
78. Hsiue G.H., Hsu S.H., Yang C.C.. Preparation of controlled release ophthalmic drops,for glaucoma therapy using thermosensitive poly(N-isopropylacrylamide. Biomaterials 2002; 23:457-462.
79. Ben-Yosef R., Gipps M., Zeira M.. Hyperthermia and liposomal encapsulated doxorubicin. Isr. Med. Assoc. J.2003; 5:407-409.
80. Kong G., Braun R.D., Dewhirst M.W.. Characterization of the effect of hyperthermia on nanoparticle extravasation from tumor vasculature. Cancer. Res. 2001; 61:3027-3032.
81. Chilkoti A., Dreher M.R., Meyer D.E.. Targeted drug delivery by thermally responsive polymers. Adv. Drug Deliv. Rev.2002; 54:613-630.
82. Kim E.J, Cho S.H., Yuk S.H.. Polymeric microspheres composed of pH/temperature-sensitive polymer complex. Biomaterials 2001; 22:2495-2499.
83. Ma L.W., Liu M.Z., Liu H.L., Chen J., Cui D.P.. In vitro cytotoxicity and drug release properties of pH-and temperature-sensitive core-shell hydrogel microspheres. Inter. J. Pharm.2010; 385:86-91.
84. Ma L.W., Liu M.Z., Liu H.L., Chen J., Gao C.M., Cui D.P.. Dual crosslinked pH-and temperature-sensitive hydrogel beads for intestine-targeted controlled release. Polym. Adv. Tech.2010; 21:348-355.
85. Zhang K.,Wu X.Y.. Modulated insulin permeation across a glucose-sensitive polymeric composite membrane. J. Control. Release 2002; 80:169-178.
86. Qiu Y., Park K.. Environment-sensitive hydrogels for drug delivery. Adv. Drug Deliv. Rev.2001; 53:321-339.
87. KimJ J., Park K.. Glucose-binding property of pegylated concanavalina. Pharm. Res.2001; 18:794-799.
88. Kataoka K., Miyazaki H., Bunya M.. Totally synthetic polymer gelsresponding to external glucose concentration:Their preparation and application to on-off regulation of insulin release. J. Am. Chem. Soc.1998; 120:12694-12695.
89. Gayathri V.P.. Biopolymer albumin for diagnosis and in drug delivery. Drug Develop. Res.2003; 58:219-247.
90. Walline K.S., van Buren K., Ratner B.D.. Synthesis of thrombinresponsive drug delivery coating for cardiovascular stents. Polym. Prep.2003; 44:193-194.
91. Lee K.Y., Peters M.C., Anderson K.W.. Controlled growthfactor release from synthetic extracellular matrices. Nature 2000; 408:998-1000.
92. Santini J.T., Cima M.J., Langer R.. A controlled release microchip. Nature 1999; 397:335-338.
93. Budi A., Legge F.S., Treutlein H.. Electric field effects on insulin chain-B conformation. J. Phys. Chem B.2005; 109:22641-22648.
94. Kwon I.C., Bae Y.H., Kim S.W.. Electrically erodible polymer gel for controlled release of drugs. Nature 1991; 354:291-293.
95. Lever I.J., Bradbury E.J., Cunningham J.R.. Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation. J. Neurosci 2001; 21:4469-4477.
96.韩济生.能否通过外周电刺激引起中枢神经肽的释放.北京大学学报：医学版2002：34：408-413.
97. Thieme T.. Microchips and micromuscles could spell the end of one-size-fits-all medicine. Discover 2001; 22:28-30.
98. Alexiou C., Arnold W., Klein R.J.. Locoregional cancer treatment with magnetic drug targeting. Cancer. Res.2000; 60:6641-6648.
99. Kubo T., Sugita T., Shimose S.. Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamycin for osteosarcoma inhamsters. Int. J. Oncol.2001; 18:121-125.
100. Koda J., Li H., Qin S.. Interim results from a phase Ⅰ/Ⅱ study of hepatic delivery of doxorubicin adsorbed to magnetic targeted carriers (MTC2DOX) in patients with unresectable HCC. San Francisco:Joy Koda,2004.
101. Mykhaylyk O., Cherchenko A., Ilkin A.. Glial brain tumor targeting of magnetite nanoparticles in rats. J. Magn. Magn. Mater.2001; 225:241-247.
102. Wong J., Mukherjee D., Porter T.. Ultrasound enhances PESDA linked oligonucleotide deposition into myocardial tissue. J. Am. Soc. Echo.1998; 11: 498-455.
103. Shohet R.V., Chen S.,.Zhou Y.T.. Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation 2000; 101: 2554-2556.
104. Unger E.C.,Hersh E.,Vannan M.. Gene delivery using ultrasound contrast agents. Echocardiography 2001; 18:355-361.
105. Heller J., Baker R.W., Gale R.M.. Controlled drug release by polymer dissolution. I. Partial esters of maleic anhydride copolymers-properties and theory.J. Appl. Polym. Sci.1978; 22:1991-2009.
106. Kazuhiko I.N.. Preparation and permeability of urea-responsive polymer membrane consisting of immobilized urease and poly(aromatic carboxylic acid). J. Polym. Sci. Part C:Polym. Letter.1985; 23:531-535.
107. Schwartz M., Kossmann H.. Acrylic and acrylic/styrene copolymer dispersions. European Coating J.1998; 3:134-140.
108.范浩军,安州.聚氨酯-丙烯酸树脂互穿网络皮革涂饰剂研究.中国皮革1997；26：10-13。
109.李合成,李旭东,杨丽等.核-壳型聚合物乳液对照像性能的促进和稳定作用.影像技术2002；4：29-31.
110. Weissman J.M., Sunkara H.B., Tse A.S.. Thermally Switchable Periodicities and Diffraction from Mesoscopically Ordered Materials. Science 1996; 274: 959-963.
111. Singh M., Singh O., Talwar G.P.. Biodegradable delivery system for a birth control vaccine:Immunogenicity studies in rats and monkeys. Pharm. Res.1995; 12:1796-1800.
112. Wang D.G., Zheng H., Hu Y.J.. Corrections for Contour Irregularities of Human Body. Beijing Bio. Eng.1995; 14:173-177.
113. Bastos-Gonzales D., Ortega-Vinuesa J.L., De Las Nieves F.J., Hidalgo-Alvarez R.. Synthesis and characterization of peptide-functionalized polymeric nanoparticles.J. Colloid. Int. Sci.,1995; 176:232-247.
114. Lee C.F.,Young T.H., Huang Y.H., Chiu W.Y.. Synthesis and properties of polymer latex with carboxylic acid functional groups for immunological studies. Polymer 2000; 41:8565-8571.
115. Kondo A., Fukuda H.. Preparation of thermo-sensitive magnetic microspheres and their application to bioprocesses. Colloid Surface A 1999; 153:435-438.
116. Chen J.P., Su D.R. Development of Functional Temperature-Responsive Poly(styrene-co-N-isopropylacrylamide) microspheres. J. Chin. Inst. Chem. Eng.2001; 32:241-251.
117. Santos R.M, Forcada J.. Acetal-functionalized polymer particles useful for immunoassays.J. Polym. Sci. Part A:Polym. Chem.1997; 35:1605-1610.
118.任广智,李振华,何炳林.磁性壳聚糖微球用于脲激酶的固定化研究.磁性壳聚糖微球的制备和表征.离子交换与吸附2001；17：224-229.
119.贾文娟.药物缓释微球的制备、表征及性能研究,2007.
120.姚帮新,邹烨,阙俐.改良溶剂挥发／萃取法制备曲尼司特聚乳酸微球及体外表征.中国药学杂志2006；41：608-610.
121. Lee U., Park J., Yank E.H.. Investigation of the factors influencing the releaserates of cyclosporin loaded micro-and nanoparticles prepared by high-pressurehomogenizer. J. Control. Release 2002; 84:115-123.
122. Zhu K.J., Zhann J.X., Warm C.. Preparation and in vitro release behaviour of 5-fluorouracil-loaded microspheres based on poly (L-lactide) and its carbonatecopolymers. J. Microencapsul2003; 20:731-743.
123. Aguiar M.M.G, Rodrigues J.M., Silva C.A.. Encapsulation of insulin-cyclodextrin complex in PLGA microspheres:A new approach for prolonged pulmonary insulindelivery. J. Microencapsul 2004; 21:553-564.
124. Wong H.M., Wang J.J., Wang C.. In Vitro Sustained Release of Human Immunoglobulin G from Biodegradable Microspheres, Ind. Eng. Chem. Res. 2001; 40:933-948.
125. Ywujang F., Shinshing S., Fuhu S.. Development of biodegradable PLGA microspheres for the controlled release of 5-FU by the sp ray drying method.
Colloid Surface A 2002; 6:269-279.
126.刘善奎,钟延强,王芳等.口蹄疫DNA疫苗海藻酸钠微球的制备及体外释放研究.药学服务与研究2004；4：107-111.
127. Maryellen S., David E., PaulaW.. Effect of p roteinmolecular weight on release from micron-sized PLGA microspheres. J. Control.Release 2001; 76:297-311.
128. Fwulong M., Shinshing S., Yimei L.. Chintin/PLGA blend microspheres as a biodegradable drug delivery system:a new delivery system for p rotein. Biomaterials 2003; 11:5023-5036.
129. Ywujang F., Shinshing S., Fuhu S.. Development of biodegradable copoly(lactic/glycolic acid) microspheres for the controlled release of 5-FU by the sp ray dryingmethod. Colloid Surface B 2002; 4:269-279.
130. Carrasguillo K.G., Stanley A.M., Aponte-Carro J.C.. Non-aqueous encap sulation of excip ient stabilizedsp ray-freeze dried BSA into poly(lactide-co-lycolide) microspheres results in release of native p rotein. J. Control. Release 2001; 3:199-208.
131.朱晓丽,顾相伶,张志国.单凝聚与复凝聚法制备昆虫激素十二醇微胶囊及其释放行为.高分子学报2007；5：491-494.
132.敦洁宁,邓树海,苗彩云.大蒜素壳聚糖微球的研究.山东大学学报：医学版2005；43：452-454.
133.刘利萍,李苹,吴泽志.5-FU壳聚糖／丝素复合磁微球的制备及体外性质研究.中国药学杂志2003；38：774-777.
134. Green B.K., Schleicher L., U.S. Pat.1956; 2,730:456-457.
135. Ranney M.W.. "Microencapsulation Technology", Noyes Development, ParkRidge, NJ,1969.
136. Gutchko M.H.. "Microcapsules and Microencapsulation Techniques", Noyes Data, Park Ridge, NJ,1976.
137. Yolles S., Leafe D.I., Meyer F.J.. Timed-release depot for anticancer agents.J. Pharm. Sci.1975; 64:115-116.
1. Qu X., Wirsen A., Albertsson A.C.. Novel pH-sensitive chitosan hydrogels: swelling behavior and states of water. Polymer 2000; 41:4589-4598.
2. Paula H.C.B., Gomes F.J.S., Paula R. C.M.. Swelling studies of chitosan/cashew nut gum physical gels.Carbohyd. Polym.2002; 48:313-318.
3. Alvarez-Lorenzo C., Concheiro A.. Reversible adsorption by a pH-and temperature-sensitive acrylic hydrogel. J. Control. Release 2002; 80:247-257.
4. Lubben I.M., Verhoef J.C., Borchard G., Junginger H.E.. Chitosan and its derivatives in mucosal drug and vaccine delivery. Eur. J. Pharm. Sci.2001; 14: 201-207.
5. Hejazi R., Amiji M.. Chitosan-based gastrointestinal delivery systems.J. Control. Release 2003; 89:151-165.
6. Prabaharan M., Mano J.F.. A novel pH and thermo-sensitive N,O-carboxymethyl. chitosan-graft-poly(N-isoproylacrylamide) hydrogel for controlled drug delivery e-Polymers,2007; 043:1-14.
7. El-Tahlawy K.F., El-Rafie S.M., Aly A.S.. Preparation and application of chitosan/poly(methacrylic acid) graft copolymer. Carbohyd. Polym.2006; 66: 176-183.
8. El-Tahlawy K., Hudson S.M.. Graft copolymerization of hydroxyethyl methacrylate onto chitosan. J. Appl. Polym. Sci.2001; 82:683-702.
9. Fu G.Q., Li H.Y., Yu H. F., Liu L., Yuan Z., He B.L.. Synthesis and lipoprotein sorption properties of porous chitosan beads grafted with poly(acrylic acid). React. Funct. Polym.2006; 66:239-246.
10. Fu G.Q., Zhao J.C., Yu H., Liu L., He B.L.. Bovine serum albumin-imprinted polymer gels prepared by graft copolymerization of acrylamide on chitosan. React. Funct. Polym.2007; 67:442-450.
11. Santos K.S.C.R.D., Coelho J.F.J., Ferreira P., Pinto I., Lorenzetti S.G., Ferreira E.I., Higa O.Z., Gil M.H.. Synthesis and characterization of membranes obtained by graft copolymerization of 2-hydroxyethyl methacrylate and acrylic acid onto chitosan. Int. J. Pharm.2006; 310:37-45.
12. Yazdani-Pedram M., Retuer J., Quijada R.. Hydrogels based on modified chitosan, 1 Synthesis and swelling behavior of poly(acrylic acid) grafted chitosan. Macromol Chem. Phys.2000; 201:923-930.
13. Jiang H.L., Kim Y.K., Arote R., Nah J.W., Cho M.H., Choi Y.J., Akaike T., Cho C.S.. Chitosan-graft-polyethylenimine as a gene carrier. J. Control. Release 2007; 117:273-280.
14. Yazdani-Pedram M., Retuert J.. Homogeneous grafting reaction of vinyl pyrrolidone onto chitosan. J. Appl. Polym. Sci.1997; 63:1321-1326.
15. Prabaharan M., Gong S.Q.. Novel thiolated carboxymethyl chitosan-g-b-cyclodextrin as mucoadhesive hydrophobic drug delivery carriers. Carbohyd. Polym.2008; 73:117-125.
16. Chen X.G., Wang Z., Liu W.S., Park H. J.. The effect of carboxymethyl-chitosan on proliferation and collagen secretion of normal and keloid skin fibroblasts. Biomaterials 2002; 23:4609-4614.
17. Li Z., Zhuang X.P., Liu X.F., Guan Y.L., Yao K.D.. Study on antibacterial O-carboxymethylated chitosan/cellulose blend film from LiCl/N,N-dimethylacetamide solution. Polymer 2002; 43:1541-1547.
18. El-Gendy E.H., Ali N.M., El-Shanshoury I.A.. Processes involved during radiation grafting of N-vinyl pyrrolidone onto poly(ethylene terephthatate) fabric. J. Appl. Polym. Sci.2006; 101:3009-3013.
19. Elassar A.A., El-Sawy N.M.. Recent developments in the radiation grafting of N-vinyl-2-pyrrolidone onto low-density polyethylene with cinnamonitrile derivatives. J. Appl. Polym. Sci.2005; 95:1189-1197.
20. Kim J.J., Park K.. Modulated insulin delivery from glucose-sensitive hydrogel dosage forms. J. Control. Release 2001; 77:39-47.
21. Berger J., Reist M., Mayer J. M., Felt O., Peppas N.A., Gurny R.. Structure and
interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications.Eur.J. Pharm. Biopharm.2004; 57:19-34.
22. Berger J., Reist M., Mayer J.M., Felt O., Gurny R.. Structure and interaction in chitosan hydrogels formed by complexation of aggregation for biomedical applications. Eur. J. Pharm. Biopharm.2004; 57:35-52.
23. Prabaharan M., Reis R.L., Mano J.F.. Carboxymethyl chitosan-graft-phosphatidylethanolamine:Amphiphilic matrices for controlled drug delivery. React. Funct. Polym.2007; 67:43-52.
24. Wheatley M.A., Chang M., Park E., Langer R.. Coated alginate microspheres: Factors influencing the controlled delivery of macromolecules. J. App.l Polym. Sci. 1991; 43:2123-2135.
25. Ma J.H., Zhang L., Fan B., Xu Y., Liang B.R.. A novel sodium carboxymethylcellulose/poly(N-isopropylacrylamide)/Clay semi-IPN nanocomposite hydrogel with improved response rate and mechanical properties J. Polym. Sc.i Part B:Polym. Phys.2008; 46:1546-1555.
26. Prabaharan M., Mano J. F.. Chitosan-graft-polyethylenimine as a gene carrier. Macromol. Biosci.2005; 5:965-973.
27. Lee C.F., Wen C.J., Chiu W.Y.. Synthesis of poly(chitosan-N-isopropylacrylamide) complex particles with the method of soapless dispersion polymerization. J. Polym. Sci. Part A:Polym. Chem.2003; 41: 2053-2063.
28. Qian F., Cui F.Y., Ding J.Y., Tang C., Yin C.H.. Chitosan graft copolymer nanoparticles for oral protein drug delivery:preparation and characterization. Biomacromolecules 2006; 7:2722-2727.
29. Mahdavinia G.R., Pourjavadi A., Hosseinzadeh H., Zohuriaan M.J.. Modified chitosan 4. Superabsorbent hydrogels from poly(acrylic acid-co-acrylamide) grafted chitosan with salt-and pH-responsiveness properties. Eur. Polym. J.2004; 40:1399-1407.
30. Isiklan N., Inal M., Yigitoglu M.. Synthesis and haracterization of poly(N-vinyl-2-pyrrolidone) grafted sodium alginate hydrogel beads for the controlled release of indomethacin. J. Appl. Polym. Sci.2008; 110:481-493.
31. Chauhan G.S., Singh B., Kumar S.. Synthesis and characterization of N-vinyl pyrrolidone and cellulosics based functional graft copolymers for use as metal ions and iodine sorbents. J. Appl. Polym. Sci.2005; 98:373-382.
32. Yazdani-Pedram M., Retuert J.. Homogeneous grafting reaction of vinyl pyrrolidone onto chitosan. J. Appl. Polym. Sci.1997; 63:1321-1326.
33. Wang Y.S., Liu L.R., Weng J., Zhang Q.Q.. Preparation and characterization of self-aggregated nanoparticles of cholesterol-modiwed O-carboxymethyl chitosan conjugates. Carbohyd. Polym.2007; 69:597-606.
34. Xie W.M., Xu P.X., Liu Q.. Antioxidant activity of water-soluble chitosan derivatives. Bioorg. Med. Chem. Lett.,2001; 11:1699-1701.
35. Chen S.L., Liu M.Z., Jin S.P., Chen Y.. Synthesis and swelling properties of pH sensitive hydrogels based on chitosan and poly(methacrylic acid) semi-interpenetrating polymer network. J. Appl. Polym. Sci.2005; 98:1720-1726.
36. Chen S.L., Liu M.Z., Jin S.P., Chen Y.. Structure and properties of the polyelectrolyte complex of chitosan with poly(methacrylic acid). Polym. Int.2007; 56:1305-1312.
37. Huang M.F., Jin X., Li Y.. Fang Y.E. Syntheses and characterization of novel pH-sensitive graft copolymers of maleoylchitosan and poly(acrylic acid). React. Funct. Polym.2006; 66:1041-1046.
38. Rokhade A.P., Patil S.A., Aminabhavi T.M.. Synthesis and characterization of semi-interpenetrating polymer network microspheres of acrylamide grafted dextran and chitosan for controlled release of acyclovir. Carbohyd. Polym.2007; 67:605-613.
39. Agnihotri S.A., Aminabhavi T.M.. Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine. Int. J. Pharm.2006; 324:103-115.
40. Kudaibergenov S.E., Sigitov V.B.. Swelling, shrinking, deformation, and oscillation of polyampholyte gels based on vinyl 2-aminoethyl ether and sodium acrylate. Langmuir 1999; 15:4230-4235.
41. Ritger P.L., Peppas N.A.. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices.J. Control. Release 1987; 5:37-42.
42. Peppas N.A., Bures P., Leobandung W., Ichikawa H.. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm.2000; 50:27-46.
43. Singh B., Chauhan G.S., Sharma D.K., Kant A., Gupta I., Chauhan N.. The release dynamics of model drugs from the psyllium and N-hydroxymethylacrylamide based hydrogels. Int. J. Pharm.2006; 325:15-25.
1. Yamada K., Furuya A., Akimoto M., Maki T., Suwa T., Ogata H.. Evaluation of gastrointestinal transit controlled-beagle dog as a suitable animal model for bioavailability testing of sustained-release acetaminophen dosage form. Int. J. Pharm.1995; 119:1-10.
2. Khan M.Z., Stedul H.P., Kurjakovic N.. A pH dependent colon-targeted oral drug delivery system using methacrylic acid copolymers. Ⅱ. Manipulation of drug release using Eudragit(?) L100 and Eudragit(?) S100 combinations. Drug Dev. Ind. Pharm.2000; 26:549-554.
3. Steed K.P., Hooper G., Monti N., Strolin Benedetti M., Fornasini G., Wilding I.R. The use of pharmacoscintigraphy to focus the development strategy for a novel 5-ASA colon targeting system ("TIME CLOCK"(?) system).J. Control. Release 1997; 49:115-122.
4. Hu Z.P., Kimura G., Mawatari S., Shimokawa T., Yoshikawa Y., Takada K.. New preparation method of intestinal pressure-controlled colon delivery capsules by coating machine and evaluation in beagle dogs. J. Control. Release 1998; 56: 293-302.
5. Fukui E., Miyamura N., Uemura K., Kobayashi M.. Preparation of enteric coated timed-release press-coated tablets and evaluation of their function by in vitro and in vivo tests for colon targeting. Int. J. Pharm.2000; 204:7-15.
6. Jeong Y.I., Ohno T., Hu Z., Yoshikawa Y., Shibata N., Nagata S., Takada K.. Evaluation of an intestinal pressure-controlled colon delivery capsules prepared by a dipping method. J. Control. Release 2001; 71:175-182.
7. Tozaki H., Komoike J., Tada C., Maruyama T., Terabe A., Suzuki T., Yamamoto A, Muranishi S.. Chitosan capsules for colon-specific drug delivery:improvement of insulin absorption from the rat colon. J. Pharm. Sci.1997; 86:1016-1021.
8. Kakoulides E.P., Smart J.D., Tsibouklis J.. Azocrosslinked poly(acrylic acid) for colonic delivery and adhesion specificity:synthesis and characterization.J. Control. Release 1998; 52:291-300.
9. Xu Y.M., Zhan C.Y., Fan L.H., Wang L., Zheng H.. Preparation of dual crosslinked alginate-chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system. Int. J. Pharm.2007; 336:329-337.
10. Ahrabi S.F., Madsen G., Dyrstad K., Sande S.A., Graffner C.. Development of pectin matrix tablets for colonic delivery of model drug ropivacaine. Eur. J. Pharm. Sci.2000; 10:43-52.
11. Semde R., Amighi K., Devleeschouwer M.J., Moes A.J.. Studies of pectin HM/Eudragit(?) RL/Eudragit(?) NE film-coating formulations intended for colonic drug delivery. Int. J. Pharm.2000; 197:181-192.
12. Ravi V., Siddaramaiah T. M.. Pramod Kumar. Influence of natural polymer coating on novel colon targeting drug delivery system. J. Mater. Sci:Mater. Med. 2008; 19:2131-2136.
13. Chen J., Liu M.Z., Jin S.P., Liu H.L.. Synthesis and characterization of k-carrageenan/poly(N,N-diethylacrylamide) semi-interpenetrating polymer network hydrogels with rapid response to temperature. Polym. Adv. Technol.2008; 19: 1656-1663.
14. Chen L.Y., Tian Z.G., Du Y.M.. Synthesis and pH sensitivity of carboxymethyl chitosan-based polyampholyte hydrogels for protein carrier matrices. Biomaterials 2004; 25:3725-3732.
15. Prabaharan M., Mano J.F.. Hydroxypropyl chitosan bearing b-cyclodextrin cavities:synthesis and slow release of its inclusion complex with a model hydrophobic drug. Macromol. Biosci.2005; 5:965-973.
16. Lin Y.W., Chen Q., Luo H.B.. Preparation and characterization of N-(2-carboxybenzyl)chitosan as a potential pH-sensitive hydrogel for drug delivery, Carbohyd. Res.2007; 342:87-95.
17. Lin Y.H., Liang H.F., Chung C.K., Chen M.C., Sung H.W.. Physically crosslinked alginate/N,O-carboxymethyl chitosan hydrogels with calcium for oral delivery of protein drugs. Biomaterials 2005; 26:2105-2113.
18. Panayiotou M., Pohner C., Vandevyver C., Wandrey C., Hilbrig F., Freitag R.. Synthesis and characterisation of thermo-responsive poly(N,N-diethylacrylamide) microgels. Reac. Funct Polyme.2007; 67:807-819.
19. Panayiotou M., Freitag R.. Synthesis and characterisation of stimuli-responsive poly(N,N'-diethylacrylamide) hydrogels. Polymer 2005; 46:615-621.
20. Shibanuma T., Aoki T., Sanui K., Ogata N., Kikuchi A., Sakurai V., Okano T.. Thermosensitive phase-separation behavior of poly(acrylic acid)-graft-poly(N,N-dimethylacrylamide) aqueous solution. Macromolecules 2000; 33:444-450.
21. Lee C.F., Wen C.J., Chiu W.Y.. Synthesis of Poly(chitosan-N-isopropylacrylamide) complex particles with the method of soapless dispersion polymerization. J. Polym. Sci. Part A:Polym. Chem.2003; 41: 2053-2063.
22. Qian F., Cui F.Y., Ding J.Y., Tang C., Yin C.H.. Chitosan graft copolymer nanoparticles for oral protein drug delivery:preparation and characterization. Biomacromolecules 2006; 7:2722-2727.
23. Brugnerotto J., Lizardi J., Goycoolea F.M., Arguelle-Monal W., Desbrieres J., Rinaudo M.. An infrared investigation in relation with chitin and chitosan characterization. Polymer 2001; 42:3569-3580.
24. Sarkyt E.K., Vladimir B.S.. Swelling, shrinking, deformation, and oscillation of polyampholyte gels based on vinyl N-aminoethyl ether and sodium acrylate. Langmuir 1999; 15:4230-4235.
25. Chen S.C., Wu Y.C., Mi F.L., Lin Y.H., Yu L.C., Sung H.W.. A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. J. Control. Release 2004; 96: 285-300.
26. Moura D.M.R., Guilherme M.R., Campese G.M.. Porous alginate-Ca2+hydrogels interpenetrated with PNIPAAm networks:Interrelationship between compressive stress and pore morphology. Eur. Polym. J.2005; 41:2845-2852.
27. Liu H.L., Liu M.Z., Jin S.P., Chen S.L.. Synthesis and characterization of fast responsive thermo-and pH-sensitive poly[(N,N-diethylacrylamide)-co-(acrylic acid)] hydrogels. Polym. Int.2008; 57:1165-1173.
28. Agnihotri S.A., Aminabhavi T.M.. Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine. Int. J. Pharm.2006; 324:103-115.
29. Zhang X.Z., Wu D.Q., Chu C.C.. Synthesis, characterization and controlled drug release of thermosensitive IPN-PNIPAAm hydrogels. Biomaterials 2004; 25: 3793-3805.
30. Ritger P.L., Peppas N.A.. A simple equation for description of solute release. II Fickian and anomalous release from swellable devices. J. Control. Release 1987; 5:37-42.
31. Peppas N.A., Bures P., Leobandung W., Ichikawa H.. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm.,2000; 50,27-46.
32. Tapia C., Corbalan V., Costa E., Gai M.N., Yazdani-Pedram M.. Study of the release mechanism of diltiazem hydrochloride from matrices based on chitosan-alginate and chitosan-carrageenan mixtures. Biomacromolecules 2005; 6: 2389-2395._
33. Chen S.L., Liu M.Z., Jin S.P., Wang B.. Preparation of ionic-crosslinked chitosan-based gel beads and effect of reaction conditions on drug release behaviors. Int. J. Pharm.2008; 349:180-187.
34. Nochos A., Douroumis D., Bouropoulos N.. In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads. Carbohyd. Polym.2008; 74: 451-457.
1. Chen X., Cui Z.C., Chen Z.M., Zhang K., Lu G., Zhang G., Yang B.. The synthesis and characterizations of monodisperse cross-linked polymer microspheres with carboxyl on the surface. Polymer 2002; 43:4147-4152.
2. Lee I.S., Cho M.S., Choi H.J.. Preparation of polyaniline coated poly(methyl methacrylate) microsphere by graft polymerization and its electrorheology. Polymer 2005; 46:1317-1321.
3. Kima J.W., Leeb J. E., Kima S.J., Leea J.S., Ryub J.H., Kima J., Hana S.H., Changa I.S., Suh K.D.. Synthesis of silver/polymer colloidal composites from surface-functional porous polymer microspheres. Polymer 2004; 45:4741-4747.
4. Kimura K., Kohama S., Yamashita Y., Uchida T., Sakaguchi Y.. Diameter control of poly(poxycinnamoyl) microspheres prepared by self-organizing polycondensation. Polymer 2003; 44:7383-7387.
5. Jones C.D., Lyon L.A.. Synthesis and characterization of multiresponsive core-shell microgels. Macromolecules 2000; 33:8301-8306.
6. Jones C.D., Lyon L.A.. Shell-restricted swelling and core Compression in poly(N-isopropylacrylamide) core-shell microgels. Macromolecules 2003; 36: 1988-1993.
7. Leobandung W., Ichikawa H., Fukumori Y., Peppas N.A.. Monodisperse nanoparticles of poly(ethylene glycol) macromers and N-isopropyl acrylamide for biomedical applications. J. Appl. Polym. Sci.2003; 87:1678-1684.
8.Ichikawa H., Fukumori Y.. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethyl cellulose matrix. J. Controlled Release 2000; 63:107-119.
9. Vihola H., Laukkanen A., Hirvonen J., Tenhu H.. B inding and release of drugs into and from thermosensitive poly(N-vinyl caprolactam) nanoparticles. Eur. J. Pharm. Sci.2002; 16:69-74.
10. Kawaguchi H., Fujimoto K.. Smart latexes for bioseparation. Bioseparation 1998; 7:253-258.
11. Panchapakesan B., DeVoe D.L, Widmaier M.R., Cavicchi R., Semancik S.. Nanoparticle engineering and control of tin oxide microstructures for chemical microsensor applications. Nanotechnology 2001; 12:336-349.
12. Bergbreiter D.E., Case B.L., Liu Y.S., Caraway J.W.. Poly(N-isopropylacrylamide) soluble polymer supports in catalysis and synthesis. Macromolecules 1998; 31: 6053-6062.
13. Guiseppi-Elie A., Sheppard N.F., Brahim S., Narinesingh D.. Enzyme microgels in packed-bed bioreactors with downstream amperometric detection using microfabricated interdigitated microsensor electrode arrays. Biotechnol. Bioeng. 2001; 75:475-484.
14. Irene B., Catherine D., Patrick C. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Delivery Rev.2002; 54:631-651.
15. Lee T.H., Wang J., Wang C.H.. Double-walled microspheres for the sustained release of a highly water soluble drug:characterization and irradiation studies. J. Control. Release 2002; 83:437-452.
16. Yang Y.Y., Shi M., Goh S.H., Moochhala S.M., Ng S., Heller J.. P OE/PLGA composite microspheres:formation and in vitro behavior of double walled microspheres. J. Control. Release 2003; 88:201-213.
17. Berkland C., Cox A., Kim K.K., Pack D.W.. Three-month, zero-order piroxicam release from monodispersed double-walled microspheres of controlled shell thickness. J. Biomed. Mater. Res.2004; 70A:576-584.
18. Marilia P., Ruth F.. Synthesis and characterisation of stimuli-responsive poly(N,N'-diethylacrylamide) hydrogels. Polymer 2005; 46:615-621.
19. Panayiotou M., Pohner C., Vandevyver C., Wandrey C., Hilbrig F., Freitag R.. Synthesis and characterisation of thermo-responsive poly(N,N-diethylacrylamide) microgels. Reac. Funct. Polym.2007; 67:807-819.
20. Wu X., Pelton R.H., Hamielec A.E., Woods D.R., McPhee W.. The kinetics of poly(N-isopropylacrylamide) microgel latex formation. Colloid Polym. Sci.1994; 272:467-477.
21. Antonietti M., Pakula T., Bremser W.. Rheology of small spherical polystyrene microgels:a direct proof for a new transport mechanism in bulk polymers besides reptation. Macromolecules 1995; 28:4227-4233.
22. Neyret S., Vincent B.. The properties of polympholyte microgel particles prepared by microemulsion polymerization. Polymer 1997; 38:6129-6134.
23.Ole Kiminta D.M., Luckham P.F., Lenon S.. The rheology of deformable and the responsive microgel particles. Polymer 1995; 36:4827-4831.
24. Wu C., Zhou S.Q.. Effects of surfactants on the phase transition of poly(N-isopropylacrylamide) in water. J. Polym. Sci. B:Polym. Phys.1996; 34: 1597-1604.
25. Chai Z.K., Zheng X., Sun X.F.. Preparation of polymer microspheres from solutions. J. Polym. Sci. B:Polym. Phys.2003; 41:159-165.
26. Xiao X.C., Chu L.Y. Chen W.M., Wang S., Xie R. Preparation of submicrometer-sized monodispersed thermoresponsive core-shell hydrogel microspheres. Langmuir 2004; 20:5247-5253.
27. Irene B., Catherine D., Patrick C.. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Delivery Rev.2002; 54:631-651.
28. Lee T.H., Wang J., Wang C.H.. Double-walled microspheres for the sustained release of a highly water soluble drug:characterization and irradiation studies. J. Control. Release 2002; 83:437-452.
29. Yang Y.Y., Shi M., Goh S.H., Moochhala S.M., Ng S., Heller J.. P OE/PLGA composite microspheres:formation and in vitro behavior of double walled microspheres. J. Control.dRelease 2003; 88:201-213.
30. Bergbreiter D.E., Case B.L., Liu Y.S., Caraway J.W.. Poly(N-isopropylacrylamide) soluble polymer supports in catalysis and synthesis. Macromolecules 1998; 31: 6053-6062.
31. Chen S.A.,Lee S.T.. Kinetics and mechanism of emulsifier-free emulsion polymerization:styrene/phydrophilic comonomer (acrylamid) system. Macromolecules 1991; 24:3340-3351.
32. Shibanuma T., Aoki T., Sanui K., Ogata N., Kikuchi A., Sakurai Y., Okano T.. Thermosensitive phase-separation behavior of poly(acrylic acid)-graft-poly(N,N-dimethylacrylamide) aqueous solution. Macromolecules 2000; 33:444-450.
33. Liu H.L., Liu M.Z., Jin S.P., Chen S.L.. Synthesis and characterization of fast responsive thermo-and pH-sensitive poly[(N,N-diethylacrylamide)-co-(acrylic acid)] hydrogels. Polym. Int.2008; 57:1165-1173.
34. Zhang X.Z., Zhuo R.X., Yang Y.Y.. Using mixed solvent to synthesize temperature sensitive poly(N-isopropylacrylamide) gel with rapid dynamics properties. Biomaterials 2002; 23:1313-1318.
35. Ritger P.L., Peppas N.A.. A simple equation for description of solute release. Ⅱ Fickian and anomalous release from swellable devices. J. Control. Release 1987; 5:37-42.
36. Gao C.M., Liu M.Z., Chen S.L., Jin S.P., Chen J.. Preparation of oxidized sodium alginate-graft-poly(2-dimethylamino ethyl methacrylate) gel beads and in vitro controlled release behavior of BSA. Int. J. Pharm.2009; 371:16-24.
1. Yoo H.S., Park T.G.. Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA-PEG block copolymer.J. Control. Release 2001; 70:63-70.
2. Shuai X.T., Ai H., Nasongkl N., Kim S., Gao J.M.. Micellar carriers based on block copolymers of poly(ε-caprolactone) and poly(ethylene glycol) for doxorubicin delivery. J. Control. Release 2004; 98:415-426.
3. Yu C.Y., Zhang X.C., Zhou F.Z., Zhang X.Z., Cheng S.X., Zhuo R.X.. Sustained release of antineoplastic drugs from chitosan-reinforced alginate microparticle drug delivery systems. Int. J. Pharm.2008; 357:15-21.
4. Jiang P., Bertone J.F., Colvin V.L.. A Lost-wax approach to monodisperse colloids and their crystals. Science 2001; 291:453-457.
5. Jin R., Cao Y., Mirkin C.A., Kelly K.L., Schatz G.C., Zheng J.G.. Photoinduced conversion of silver nanospheres to nanoprisms. Science 2001; 294:1901-1903.
6. Weda P., Trzebicka B., Dworak A., Tsvetanov C.B.. Thermosensitive nanospheres of low-density core-an approach to hollow nanoparticles. Polymer 2008; 49: 1467-1474.
7. Singh M.,Singh O.,Talwar G. P..Biodegradable Delivery System for a Birth Control Vaccine:Immunogenicity Studies in Rats and Monkeys. Pharm. Res.,1995; 12:1796-1800.
8. Bastos Gonzales D.,Ortega Vinuesa J. L., Nieves F. J.. Carboxylated latexes for covalent coupling antibodies, I. J. Colloid. Int. Sci.1995; 176:232-247.
9. Lee C. F.,Young T. H.,Huang Y. H.. Synthesis and properties of polymer latex with carboxylic acid functional groups for immunological studies. Polymer 2000; 41:8565-8571.
10. Kondo A.,Fukuda H.. Preparation of thermo-sensitive magnetic microspheres and their application to bioprocesses. Colloid and Surface A,1999;153:435-438.
11. Chen J.P.,Su D.R.. Modeling sludge as continuous mixture during thermal pyrolysis.J. Chin. Inst. Chem. Engrs.,2001; 32:241-251.
12. Santos R.M., Forcada J.. Acetal-functionalized polymer particles useful for immunoassays. J. Polym. Sci. A:Polym. Chem.,1997; 35:1605-1610.
13. Nardin C., Hirt T., Leukel J., Meier W.. Polymerized ABA triblock copolymer vesicles. Langmuir 2000; 16:1035-1041.
14. General S., Rudloff J., Thunemann A.F.. Hollow nanoparticles via stepwise complexation and selective decomplexation of poly(ethylene imine). Chem. Commun.2002; 5:534-535.
15. Gittins D.I., Caruso F.. Multilayered polymer nanocapsules derived from gold nanoparticle templates. Adv. Mater.2000; 12:1947-1949.
16. Jang J., Ha H.. Fabrication of hollow polystyrene nanospheres in microemulsion polymerization using triblock copolymers. Langmuir 2002; 18:5613-5618.
17. Tiarks F., Landfester K., Antonietti M.. Preparation of polymeric nanocapsules by miniemulsion polymerization. Langmuir 2001; 17:908-918.
18. Cheng C.J., Chu L.Y., Ren P.W., Zhang J., Hu L.. Preparation of monodisperse thermo-sensitive poly(N-isopropylacrylamide) hollow microcapsules. J. Colloid. Interface. Sci.2007; 313:383-388.
19. Lees-Haley P.R., Williams C.W.. Neurotoxicity of chronic low-dose exposure to organic solvents:A skeptical review. J. Clin. Psychol.1997;.5:699-712.
20. Yolles S., Leafe D.I., Meyer F.J.. Controlled release of biologically active compounds from bioerodible polymers. J. Pharm. Sci.,1975; 64:115-116.
21. Yu C.Y., Jia L.H., Yin B.C., Zhang X.Z., Cheng S.X., Zhuo R.X.. Fabrication of nanospheres and vesicles as drug carriers by self-assembly of alginate. J. Phys. Chem. C2008; 112:16774-16778.
22. Stops F., Fell J.T., Collett J.H.. Martini L.G.. Floating dosage forms to prolong gastro-retention-The characterisation of calcium alginate beads. Int. J. Pharm. 2008; 350:301-311.
23. Sarmento B., Ferreira D., Veiga F., Ribeiro A.. Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pre-gelation through DSC and FTIR studies. Carbohydr. Polym.2006; 66:1-7.
24. Sarmento B., Martins S., Ribeiro A., Veiga F., Neufeld R., Ferreira D.. Development and comparison of different nanoparticulate polyelectrolyte complexes as insulin carriers. Int. J. Pept. Res. Ther.2006;.12:131-138.
25. Cafaggi S., Russo E., Stefani R., Leardi R., Caviglioli G., Parodi B., Bignard G., De Totero D., Aiello C., Viale M.. Preparation and evaluation of nanoparticles made of chitosan or N-trimethyl chitosan and a cisplatin-alginate complex. J. Control. Release.2007; 121:110-123.
26. Shibanuma T., Aoki T., Sanui K., Ogata N., Kikuchi A., Sakurai V., Okano T.. Thermosensitive phase-separation behavior of poly(acrylic acid)-graft-poly(N,N-dimethylacrylamide) aqueous solution. Macromolecules 2000; 33:444-450.
27. Villa R., Folini M., Porta C.D., Valentini A., Pennati M., Daidone M.G., Zaffaronil N.. Inhibition of telomerase activity by geldanamycin and 17-allylamino,17-demethoxygeldanamycin in human melanoma cells. Carcinogenesis 2003; 24:851-859.
28. Lee C.F., Wen C.J., Chiu W.Y.. Synthesis of poly(chitosan-N-isopro-pylacrylamide) complex particles with the method of soapless dispersion polymerization. J. Polym. Sci. Part A:Polym. Chem.2003; 41:2053-2063.
29. Qian F., Cui F.Y., Ding J.Y., Tang C., Yin C.H.. Chitosan Graft Copolymer Nanoparticles for Oral Protein Drug Delivery:Preparation and Characterization. Biomacromolecules 2006; 7:2722-2727.
30. Ma L.W., Liu M.Z., Liu H.L., Chen J., Gao C.M., Cui D.P.. Dual crosslinked pH-and temperature-sensitive hydrogel beads for intestine-targeted controlled release. Polym. Adv. Technol.2010; 21:348-355.
31. Brugnerotto J., Lizardi J., Goycoolea F.M., Arguelle-Monal W., Desbrieres J., Rinaudo M.. An infrared investigation in relation with chitin and chitosan characterization. Polymer 2001; 42:3569-3580.
32. Colfen H., Antonietti M.. Crystal Design of Calcium Carbonate Microparticles Using Double-Hydrophilic Block Copolymers. Langmuir,1998; 14:582-589.
33. Colfen H., Qi L.. A Systematic Examination of the Morphogenesis of Calcium Carbonate in the Presence of a Double-Hydrophilic Block Copolymer.Chem. Eur. J.2001; 7:106-116.
34. Naka K., Tanaka Y., Chujo Y., Ito Y.. The effect of an anionic starburst dendrimer on the crystallization of CaCO3 in aqueous solution. Chem. Commun.,1999; 19: 1931-1932
35. Naka K, Tanaka Y, Chujo Y. Effect of Anionic Starburst Dendrimers on the Crystallization of CaCO3 in Aqueous Solution:Size Control of Spherical Vaterite Particles. Langmuir,2002; 18:3655-3658.
36. Quignard F. Cot D., Renzo F.D., Gerardin C. Core-shell copper hydroxide-polysaccharide composites with hierarchical macroporosity. Prog. Solid. State. Chem.2006; 34:161-169.
37. Zhang X.Z., Wu D.Q., Chu C.C.. Synthesis, characterization and controlled drug release of thermosensitive IPN-PNIPAAm hydrogels. Biomaterials 2004; 25: 3793-3805.
38. Marilia P., Ruth F.. Synthesis and characterisation of stimuli-responsive poly(N,N'-diethylacrylamide) hydrogels. Polymer 2005; 46:615-621.
39. Ma L.W., Liu M.Z., Chen J., Liu H.L., Cui D.P., Gao C.M.. Synthesis, characterization and drug release behavior of pH-responsive O-carboxymethyl chitosan-graft-poly(N-vinylpyrrolidone) hydrogel beads. Adv. Eng. Mater.2009; 11:B267-B274.
40. Ritger P.L., Peppas N.A.. A simple equation for description of solute release Ⅱ. Fickian and anomalous release from swellable devices. J. Control. Release.1987; 5:37-42.
41. Peppas N.A., Bures P., Leobandung W., Ichikawa H.. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm.2000; 50:27-46.
42. Tapia C., Corbalan V., Costa E., Gai M.N., Yazdani-Pedram M.. Study of the Release Mechanism of Diltiazem Hydrochloride from Matrices Based on Chitosan-Alginate and Chitosan-Carrageenan Mixtures. Biomacromolecules 2005; 6:2389-2395.
43. Singh B., Chauhan G.S., Sharma D.K., Kant A., Gupta I., Chauhan N.. The release dynamics of model drugs from the psyllium and N-hydroxymethylacrylamide based hydrogels. Int. J. Pharm.2006; 325:15-25.
1. Zhang L.F., Eisenberg A.. Multiple morphologies and characteristics of "crew-cut" micelle-like aggregates of polystyrene-b-poly(acrylic acid) diblock copolymers in aqueous solutions. J. Am. Chem. Soc.1996; 118:3168-3181.
2. Antonietti M., Forster S., Hartman J.. Novel amphiphilic block copolymers by polymer reactions and their use for solubilization of metal salts and metal colloids. Macromolecules 1996; 29:3800-3806.
3. Webber S.E.. Polymer micelles:an example of self-assembling polymers. J. Phys. Chem. B 1998; 102:2618-2626.
4. Yuan J.J., Li Y.S., Li S.Q.. Self-assembly of triblock copolymer PS-b-PEO-b-PS. Chem. J. Chin. Univ.2003; 24:371-373.
5. Moffitt M., Khougaz K., Eisenberg A.. Micellization of ionic block copolymers. Acc. Chem. Res.1996; 29:95-98.
6. Zhu H., Liu S.Y., Pan Q.M., Duan H.W. Jiang M.. Synthesis of amphiphilic block copolymer poly(styrene-b-acrylic acid) by atom transfer radical polymerization and its micellization. Chem. J. Chin. Univ.2002; 23:138-142.
7. Shen H.W., Eisenberg A.. Block length dependence of morphological phase diagrams of the ternary system of PS-b-PAA/dioxane/H2O.Macromolecules 2000; 33:2561-2572.
8. Bader H., Ringsdorf H., Schmidt B.. Watersoluble polymers in medicine. Angew. Makromol. Chem.1984; 123:457-485.
9. Liu J., Zeng F.. Allen C. In vivo fate of unimers and micelles of a poly (ethylene glycol)-block-poly(caprolactone) copolymer in mice following intravenous administration. Eur. J. Pharm. Biopharm.2007; 65:309-319.
10. Cgen Z., Wang Y., Feng Y.. Synthesis of hydroxyl-terminated copolymer of styrene and 4-vinylpyridine via nitroxide-mediated living radical polymerization. J. Appl. Polym. Sci.2004; 91:1842-1847.
11. Lee J.M., K. Lee, Min K.. The effect of polystyrene-block-poly(4-vinylpyridine) p repared by a RAFT method in the dispersion polymerization of styrene. Curr. Appl. Phys.2008; 8:732-735.
12. Luo X., Zhuang Y., Zhao X.. Controlled/living radical polymerization of styrene catalyzed by cobaltocene. Polymer 2008; 49:3457-3461.
13. Man H., Qiao X., Ming C.. Synthesis of amphiphilic block copolymer by atom transfer radical polymerization. J. South. Yangtze. Uni.2004; 3:79-82.
14. Samson A., Jenekhe X., Chen L.. Self-assembled aggregates of rodcoil block copolymers and their solubilization and encap sulation of fullerenes. Science 1998; 279:1903-1907.
15. Wang J.S., Matyjaszewski K.. Controlled/"living" radical polymerization. atom transfer radical polymerization in the presence of transition-metal complexes. J. Am. Chem. Soc.1995; 117:5614-5615.
16. Kato M., Kamigaito M., Sawamoto M., Higashimura T.. Polymerization of methyl methacrylate with the carbon tetrachloride/dichlorotris-(triphenylphosphine)ruthenium(Ⅱ)/Methylaluminum bis(2,6-di-tert-butylphenoxide) initiating system:possibility of living radical polymerization. Macromolecules 1995; 28:1721-1723.
17. Hua M., Yang W., Xue Q., Chen M.Q., Liu X.Y., Yang C.. Study on Synthesis of Amphiphilic PS-b-PMAA and Their Micellization. Acta. Chim. Sinica.2005,63, 63-67.
18. Wei L.H., Zhang W.C., Chen Y.. The Synthesis of amphophilic diblok copolymer PS-b-PAA and its morphology, nano-size aggregate formation in solutions. Acta Polym. Sin.2002; 4:548-551.
19. Cheng S.Y., Xu Z.S., Yuan J.J.. PS-b-PEO-b-PS triblock copolymers in aqueous micellization. Acta. Chim. Sinica.2000; 58:368-370.
20. Shibanuma T., Aoki T., Sanui K., Ogata N., Kikuchi A., Sakurai V., Okano T. Thermosensitive phase-separation behavior of poly(acrylic acid)-graft-poly(N,N-dimethylacrylamide) aqueous solution. Macromolecules 2000; 33:444-450.
21. Ma L.W., Liu M.Z., Liu H.L., Chen J., Cui D.P.. In vitro cytotoxicity and drug release properties of pH-and temperature-sensitive core-shell hydrogel microspheres. Inter. J. Pharm.2010; 385:86-91.
22. Ma L.W., Liu M.Z., Liu H.L., Chen J., Gao C.M., Cui D.P.. Dual crosslinked pH-and temperature-sensitive hydrogel beads for intestine-targeted controlled release. Polym. Adv. Tech.2010; 21:348-355.
23. Cao Z.Q., Liu W.G., Ye G.X., Zhao X.L., Lin X.Z., Gao P., Yao K. D.. N-isopropylacrylamide/2-hydroxyethyl methacrylate star diblock copolymers: synthesis and thermoresponsive behavior. Macromol. Chem. Phys.2006; 207: 2329-2335.
24. Badiger M.V., Rajamohanan P.R., Kulkarni M.G., Ganapathy S., Mashelkar R.A.. Proton MASS-NMR:a new tool to study thermoreversible transition in hydrogels. Macromolecules 1991; 24:106-111.
25. Nagasaki Y., Okada T., Scholz C., Iijima M., Kato M, Kataoka K.. The reactive polymeric micelle based on an aldehyde-ended poly(ethylene glycol)/poly(lactide) block copolymer. Macromolecules 1998; 31:1473-1479.
26. Weaver J.V.M., Bannister I., Robinson K.L., Bories-Azeau X., Armes S.P., Smallridge M., McKenna P.. Stimulus-responsive water-soluble polymers based on 2-hydroxyethyl methacrylate. Macromolecules 2004; 37:2395-2403.
2. Chess R.. Economic aspects of drug delivery. Pharm. Res.1998; 15:172-174.
3.姚康德,成国祥.智能材料.北京：化学工业出版社2002.
4.陈莉,主编.智能高分子材料.北京：化学工业出版社2005.
5. Fuji-Keizai. Market advanced drug delivery systems probing the route to growth. New York:Fuji-Keizai USA Inc,2005.
6.陆彬,药物新剂型与新技术.北京：人民卫生出版社2002.
7. Liu L.X., Khang G., Rhee J.M.. Monolithic osmotic tablet system for nifedipine delivery. J. Control. Release.2000; 67:309-322.
8. Lamprecht A., Yamamoto H., Takeuchi H.. Microsphere design for the colonic delivery of 5-fluorouracil.J. Control. Rel.2003; 90:313-322.
9. Okada H., Heya T., Igari Y.. One-month release injectable microspheres of leuprolide acetate inhibit steroidogenesis and genital organ growth in rats. Int. J. Pharm.1989; 54:231-239.
10. Santus G., Baker R.W. Osmotic drug delivery:a review of the patent literature. J.Control. Rel.1995; 35:1-21.
11. Theeuwes F.. Elementary Osmotic Pump. J. Pharm. Sci.1975; 64:1987-1991.
12. Langer R.. New methods of drug delivery. Science 1990; 249:1527-1533.
13. Langer R.. Transdermal drug delivery:past progress, current status, and future prospects. Adv. Drug. Deliver. Rev.2004; 56:557-558.
14. Riviere J.E., Papich M.G.. Potential and problems of developing transdermal patchesfor veterinary applications. Adv. Drug. Deliver. Rev.2001; 50:175-203.
15. Sakr F.M.. A programmable drug delivery system for oral administration. Int. J. Pharm.1999; 184:131-139.
16. Moriyama K., Yui N.. Regulated insulin release from bio-degradable hydrogels containing poly(ethylene glycol). J. Control. Release 1996; 42:237-248.
17. Shoji S., Esashi M.. Microflow devices and systems. J. Micromech. Microeng. 1994; 4:157-171.
18. Yih T.C, Wei C., Hammad B.. Modeling and characterization of a nanoliter drug-delivery MEMS micropump with circular bossed membrane. Nanomedicine 2005;1:164-175.
19. Santini J.T.J., Cima M.J., Langer R.. A controlled release microchip. Nature 1999; 397:335-338.
20.吴芳,张志荣.定时脉冲释药系统.药学进展2001；25：279-283.
21. Scherer. DDS develops "alarm clock" dose formulation. Pharm. J.1991; 24: 138-141.
22.候连兵.常用药物新剂型及临床应用.北京：人民军医出版社1998.
23. Weidner J.. System for time and/or site-specific oral drug delivery. Drug Discov. Today 2001; 6:1028-1029.
24. Gutierrez-Sanchez P.E., Hernandez-Leon A., Villafuerte-Robles L.. Effect of sodium bicarbonate on the properties of metronidazole floating matrix tablets. Drug Dev. Ind. Pharm.2008; 34:171-180.
25. Whitehead L.F., Collett J.H., Sharma H.L.. Floating drug delivery systems:an approach to oral controlled drug delivery via gastric retention. J. Control. Release 2000; 55:3-12.
26 Yang L., Chu J.S., Fix J.A.. Colon-specific drug delivery:new approaches and in vitro/in vivo evaluation. Int. J. Pharm.2002; 235:1-15.
27 Weyenberg W., Bozdag S., Foreman P.. Characterization and in vivo evaluation of ocular minitablets prepared with different bioadhesive Carbopol-starch components. Eur. J. Pharm. Biopharm.2006; 62:202-209.
28. Hoogstraate J.A.J., Wertz P.W.. Drug delivery via the buccal mucosa. Pharm. Sci. Technol. Today,1998; 1:309-316.
29. Ugwoke M.I, Agu R.U, Verbeke N.. Nasal mucoadhesive drug delivery: Background, applications, trends and future perspectives. Adv. Drug Del. Rev. 2005; 57:1640-1665.
30. King A.E, Morgan K., Sallenave J.M.. Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone. Biochem. Bioph. Res. Co. 2003; 310:594-599.
31. Bij P., Eyk A. D.. Comparative in vitro permeability of human vaginal, small intestinal and colonic mucosa. Int. J. Pharm.2003,261:147-152.
32. Wu P., Grainger D.W.. Drug/device combinations for local drug therapies and infection prophylaxis. Biomaterials 2006; 27:2450-2467.
33. Wang P.P., Frazier J., Brem H.. Local drug delivery to the brain. Adv. Drug Deliver. Rev.2002; 54:987-1013.
34. Williams J.A., Yuan X., Dillehay L.E.. Synthetic, implantable polymers for local delivery of IUdR to experimental human malignant glioma. Int. J. Radiation Oncology Biol. Phys.1998; 42:631-639.
35. Sershen S., West J.. Implantable, polymeric systems for modulated drug delivery. Adv. Drug. Deliver. Rev.2002; 54:1225-1235.
36. Langer R.. Drug delivery and targeting. Nature 1998; 392:5-10.
37. Torchilin V.P.. Drug targeting. Euro. J. Pharm. Sci.2000; 11:81-91.
38. Allen T., Moase E.H.. Therapeutic opportunities for targeted liposomal drug delivery. Adv. Drug. Deliver. Rev.1996; 21:117-133.
39. Zimmer A., Kreuter J.. Microspheres and nanoparticles used in ocular delivery systems. Adv. Drug Deliv. Rev.1995; 16:61-73.
40. Amadottir S.G., Kristmundsdottir T.. Increased dissolution rate by microencapsulation. Euro. J. Pharm. Sci.1996; 134-134.
41.朱盛山.药物新剂型.北京：化学工业出版社2003.
42. Okuhata Y.. Delivery of diagnostic agents for magnetic resonance imaging. Adv. Drug Deliv. Rev.1999; 37:121-137.
43. Zeng H., Sun S.H.. Syntheses, properties and potential applications of multicomponent magnetic nanoparticles. Adv. Funct. Mat.2008; 18:391-400.
44. Ho K.M., Li P.. Design and synthesis of novel magnetic core-shell polymeric particles. Langmuir 2008; 24:1801-1807.
45. Voltairas P;A, Fotiadis D.I, Michalis L.K.. Hydrodynamics of magnetic drug targeting. J. Biomech.2002; 35:813-821.
46. Pankhurst Q.A., Connolly J., Jones S. K.. Applications of magnetic nanoparticles in biomedicine.J. Phys. D:Appl. Phys.2003; 36:167-181.
47. Freiberg S., Zhu X.. Polymer microspheres for controlled drug release. Int. J. Pharm.2004; 282:1-18.
48. Soppirnath K.S, Aminabhavi T.M.. Water transport and drug release study from cross-linked polyacrylamide grafted guar gum hydrogel microspheres for the controlled release application. Eur. J. Pharm. Biopharm.2002; 53:87-98.
49. Soppimath K.S., Kulkarni A.R., Aminabhavi T.M.. Chemically modified polyacrylamide-g-guar gum-based crosslinked anionic microgels as pH-sensitive drug delivery systems:preparation and characterization. J. Control. Rel.2001; 75: 331-345.
50. Kurkuri M.D., Aminabhavi T.M.. Poly(vinyl alcohol) and poly(acrylic acid) sequential interpenetrating network pH-sensitive microspheres for the delivery of diclofenac sodium to the intestine. J. Control. Rel.2004; 96:9-20.
51. Wang C.H., Wang C.H., Hsiue G.H.. Polymeric micelles with a pH-responsive structure as intracellular drug carriers. J. Control. Rel.2005; 108:140-149.
52. Gillies E.R., Frechet J.M.J.. Dendrimers and dendritic polymers in drug delivery. Drug Discov. Today 2005; 10:35-43.
53. Majoros I.J, Thomas T.P, Mehta C.B.. Poly(amidoamine) Dendrimer-based multifunctional engineered nanodevice for cancer therapy. J. Med.Chem.2005; 48:5892-5899.
54. Thomas T.P., Patri A.K., Myc A.. In vitro targeting of synthesized antibody-conjugated dendrimer nanoparticles. Biomacromolecules 2004; 5: 2269-2274.
55. Low P.S., Antony A.C.. Folate receptor-targeted drugs for cancer and inflammatory diseases. Adv. Drug Deliv. Rev.2004; 56:1055-1058.
56. Thomas T.P, Majoros I.J, Kotlyar A.. Targeting and inhibition of cell growth by an engineered dendritic nanodevice. J. Med. Chem.2005; 48:3729-3735.
57. Galaev I.Y., Mattiasson B..'Smart'polymers and what they could do inbiotechnology and medicine. Trends Biotechnol.1999; 17:335-340.
58. Hoffman A.S., Stayton P.S., Bulmus V.. Really smart bioconjugatesof smart polymers and receptor proteins. J. Biomed. Mater. Res. A 2000; 52:577-586.
59. Gupta P., Vermani K., Garg S.. Hydrogels:from controlled release to pH-responsive drug delivery. Drug Discov. Today 2002; 7:569-579.
60. Kikuchi A., Okano T.. Intelligent thermoresponsive polymeric stationaryphases for aqueous chromatography of biological compounds. Prog. Polym. Sci.2002; 27: 1165-1193.
61.李小军,毕维笳,张国亮,张凤宝.刺激响应型药物释放体系的研究进展.现代化工 2006；7：57-61.
62. Torres-Lugo M., Garcia M., Record R.. pH-Sensitive hydrogels asgastrointestinal tract absorption enhancers:transport mechanisms ofsalmon calcitonin and other model molecules using the cell model. Biotechnol. Prog.2002; 18:612-616.
63. Torres-Lugo M., Garcia M., Record R.. Physicochemical behaviorand cytotoxic effects of p(methacrylic acid-g-ethylene glycol)nanospheres for oral delivery of proteins. J. Control. Release 2002; 80:197-205.
64. Singh D.K, Ray A.R. Biomedical applications of chitin, chitosan, andtheir derivatives. Rev. Macromol. Chem. Phys.2000; C40:69-83.
65. Chen S.L., Liu M.Z., Jin S.P., Wang B.. Preparation of ionic-crosslinked chitosan-based gel beads and effect of reaction conditions on drug release behaviors. Inter. J. Pharm.2008; 349:180-187.
66. Na K.,Seong L.E., Bae Y.H.. Adriamycin loaded pullulan acetate/sulfonamide conjugate nanoparticles responding to tumor pH:pH-dependentcell interaction, internalization and cytotoxicity in vitro. J. Control. Release 2003; 87:3-13.
67. Gaucher G., Fournier E., Le G.. Delivery of hydrophobic drugsthrough self-assembling nanostructures. In:Nano and Smart Systems. Toronto:University of Montreal,2004.
68. Liu L., Jin P., Zhang G.L..5-Fluorouracil loaded self-assembled and pH-sensitive nanoparticles as a novel drug carrier for treatment of malignant tumors. Chinese J. Chem. Eng.2006; 2:14-20.
69. Lee E.S., Na K., Bae Y.H.. Polymeric micelle for tumor pH and folate mediated targeting.J. Control. Release 2003; 91:103-113.
70. Lee E.S., Na K., Bae Y.H.. Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF27 tumor. J. Control. Release 2005; 103:405-418.
71. Beltran S., Hooper H.H., Blanch H.W.. Swelling equilibria for ionized temperature-sensitive gels in water and in aqueous saltsolutions.J. Chem. Phys. 1990; 92:2061-2066.
72. Chung J.E., Yokoyama M., Yamato M.. Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isop ropylacrylamide) and poly (butylmethac-rylate).J. Control. Release 1999; 62: 115-127.
73. Lyubarsky A.L., Savchenko A.B., Morocco S.B.. Mole quantity of RPE65 and its productivity in the generation of cisretinal from retinyl esters in the living mouse eye. Biochem istry 2005; 44:9880-9888.
74. Liu X.M., Yang B., Wang Y.L.. New nanoscale pulsatile drug delivery system. Chem. Mater.2005; 17:2792-2795.
75. Chung J.E.,Yokoyama M., Yamato M.. Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly (butyl methacrylate). J. Control. Release 1999; 62:115-127.
76. Sershen S.R.,Westcott S.L.,Halas N.J.. Temperature-sensitive poly(mernanoshell composites for photothermally modulated drug delivery. J. Biomed Mater.Res. 2000; 51:293-298.
77. Jeong B.,Choi Y.K., Bae Y.H.. New biodegradable polymers for injectable drug delivery systems. J. Control. Release 1999; 62:109-114.
78. Hsiue G.H., Hsu S.H., Yang C.C.. Preparation of controlled release ophthalmic drops,for glaucoma therapy using thermosensitive poly(N-isopropylacrylamide. Biomaterials 2002; 23:457-462.
79. Ben-Yosef R., Gipps M., Zeira M.. Hyperthermia and liposomal encapsulated doxorubicin. Isr. Med. Assoc. J.2003; 5:407-409.
80. Kong G., Braun R.D., Dewhirst M.W.. Characterization of the effect of hyperthermia on nanoparticle extravasation from tumor vasculature. Cancer. Res. 2001; 61:3027-3032.
81. Chilkoti A., Dreher M.R., Meyer D.E.. Targeted drug delivery by thermally responsive polymers. Adv. Drug Deliv. Rev.2002; 54:613-630.
82. Kim E.J, Cho S.H., Yuk S.H.. Polymeric microspheres composed of pH/temperature-sensitive polymer complex. Biomaterials 2001; 22:2495-2499.
83. Ma L.W., Liu M.Z., Liu H.L., Chen J., Cui D.P.. In vitro cytotoxicity and drug release properties of pH-and temperature-sensitive core-shell hydrogel microspheres. Inter. J. Pharm.2010; 385:86-91.
84. Ma L.W., Liu M.Z., Liu H.L., Chen J., Gao C.M., Cui D.P.. Dual crosslinked pH-and temperature-sensitive hydrogel beads for intestine-targeted controlled release. Polym. Adv. Tech.2010; 21:348-355.
85. Zhang K.,Wu X.Y.. Modulated insulin permeation across a glucose-sensitive polymeric composite membrane. J. Control. Release 2002; 80:169-178.
86. Qiu Y., Park K.. Environment-sensitive hydrogels for drug delivery. Adv. Drug Deliv. Rev.2001; 53:321-339.
87. KimJ J., Park K.. Glucose-binding property of pegylated concanavalina. Pharm. Res.2001; 18:794-799.
88. Kataoka K., Miyazaki H., Bunya M.. Totally synthetic polymer gelsresponding to external glucose concentration:Their preparation and application to on-off regulation of insulin release. J. Am. Chem. Soc.1998; 120:12694-12695.
89. Gayathri V.P.. Biopolymer albumin for diagnosis and in drug delivery. Drug Develop. Res.2003; 58:219-247.
90. Walline K.S., van Buren K., Ratner B.D.. Synthesis of thrombinresponsive drug delivery coating for cardiovascular stents. Polym. Prep.2003; 44:193-194.
91. Lee K.Y., Peters M.C., Anderson K.W.. Controlled growthfactor release from synthetic extracellular matrices. Nature 2000; 408:998-1000.
92. Santini J.T., Cima M.J., Langer R.. A controlled release microchip. Nature 1999; 397:335-338.
93. Budi A., Legge F.S., Treutlein H.. Electric field effects on insulin chain-B conformation. J. Phys. Chem B.2005; 109:22641-22648.
94. Kwon I.C., Bae Y.H., Kim S.W.. Electrically erodible polymer gel for controlled release of drugs. Nature 1991; 354:291-293.
95. Lever I.J., Bradbury E.J., Cunningham J.R.. Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation. J. Neurosci 2001; 21:4469-4477.
96.韩济生.能否通过外周电刺激引起中枢神经肽的释放.北京大学学报：医学版2002：34：408-413.
97. Thieme T.. Microchips and micromuscles could spell the end of one-size-fits-all medicine. Discover 2001; 22:28-30.
98. Alexiou C., Arnold W., Klein R.J.. Locoregional cancer treatment with magnetic drug targeting. Cancer. Res.2000; 60:6641-6648.
99. Kubo T., Sugita T., Shimose S.. Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamycin for osteosarcoma inhamsters. Int. J. Oncol.2001; 18:121-125.
100. Koda J., Li H., Qin S.. Interim results from a phase Ⅰ/Ⅱ study of hepatic delivery of doxorubicin adsorbed to magnetic targeted carriers (MTC2DOX) in patients with unresectable HCC. San Francisco:Joy Koda,2004.
101. Mykhaylyk O., Cherchenko A., Ilkin A.. Glial brain tumor targeting of magnetite nanoparticles in rats. J. Magn. Magn. Mater.2001; 225:241-247.
102. Wong J., Mukherjee D., Porter T.. Ultrasound enhances PESDA linked oligonucleotide deposition into myocardial tissue. J. Am. Soc. Echo.1998; 11: 498-455.
103. Shohet R.V., Chen S.,.Zhou Y.T.. Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation 2000; 101: 2554-2556.
104. Unger E.C.,Hersh E.,Vannan M.. Gene delivery using ultrasound contrast agents. Echocardiography 2001; 18:355-361.
105. Heller J., Baker R.W., Gale R.M.. Controlled drug release by polymer dissolution. I. Partial esters of maleic anhydride copolymers-properties and theory.J. Appl. Polym. Sci.1978; 22:1991-2009.
106. Kazuhiko I.N.. Preparation and permeability of urea-responsive polymer membrane consisting of immobilized urease and poly(aromatic carboxylic acid). J. Polym. Sci. Part C:Polym. Letter.1985; 23:531-535.
107. Schwartz M., Kossmann H.. Acrylic and acrylic/styrene copolymer dispersions. European Coating J.1998; 3:134-140.
108.范浩军,安州.聚氨酯-丙烯酸树脂互穿网络皮革涂饰剂研究.中国皮革1997；26：10-13。
109.李合成,李旭东,杨丽等.核-壳型聚合物乳液对照像性能的促进和稳定作用.影像技术2002；4：29-31.
110. Weissman J.M., Sunkara H.B., Tse A.S.. Thermally Switchable Periodicities and Diffraction from Mesoscopically Ordered Materials. Science 1996; 274: 959-963.
111. Singh M., Singh O., Talwar G.P.. Biodegradable delivery system for a birth control vaccine:Immunogenicity studies in rats and monkeys. Pharm. Res.1995; 12:1796-1800.
112. Wang D.G., Zheng H., Hu Y.J.. Corrections for Contour Irregularities of Human Body. Beijing Bio. Eng.1995; 14:173-177.
113. Bastos-Gonzales D., Ortega-Vinuesa J.L., De Las Nieves F.J., Hidalgo-Alvarez R.. Synthesis and characterization of peptide-functionalized polymeric nanoparticles.J. Colloid. Int. Sci.,1995; 176:232-247.
114. Lee C.F.,Young T.H., Huang Y.H., Chiu W.Y.. Synthesis and properties of polymer latex with carboxylic acid functional groups for immunological studies. Polymer 2000; 41:8565-8571.
115. Kondo A., Fukuda H.. Preparation of thermo-sensitive magnetic microspheres and their application to bioprocesses. Colloid Surface A 1999; 153:435-438.
116. Chen J.P., Su D.R. Development of Functional Temperature-Responsive Poly(styrene-co-N-isopropylacrylamide) microspheres. J. Chin. Inst. Chem. Eng.2001; 32:241-251.
117. Santos R.M, Forcada J.. Acetal-functionalized polymer particles useful for immunoassays.J. Polym. Sci. Part A:Polym. Chem.1997; 35:1605-1610.
118.任广智,李振华,何炳林.磁性壳聚糖微球用于脲激酶的固定化研究.磁性壳聚糖微球的制备和表征.离子交换与吸附2001；17：224-229.
119.贾文娟.药物缓释微球的制备、表征及性能研究,2007.
120.姚帮新,邹烨,阙俐.改良溶剂挥发／萃取法制备曲尼司特聚乳酸微球及体外表征.中国药学杂志2006；41：608-610.
121. Lee U., Park J., Yank E.H.. Investigation of the factors influencing the releaserates of cyclosporin loaded micro-and nanoparticles prepared by high-pressurehomogenizer. J. Control. Release 2002; 84:115-123.
122. Zhu K.J., Zhann J.X., Warm C.. Preparation and in vitro release behaviour of 5-fluorouracil-loaded microspheres based on poly (L-lactide) and its carbonatecopolymers. J. Microencapsul2003; 20:731-743.
123. Aguiar M.M.G, Rodrigues J.M., Silva C.A.. Encapsulation of insulin-cyclodextrin complex in PLGA microspheres:A new approach for prolonged pulmonary insulindelivery. J. Microencapsul 2004; 21:553-564.
124. Wong H.M., Wang J.J., Wang C.. In Vitro Sustained Release of Human Immunoglobulin G from Biodegradable Microspheres, Ind. Eng. Chem. Res. 2001; 40:933-948.
125. Ywujang F., Shinshing S., Fuhu S.. Development of biodegradable PLGA microspheres for the controlled release of 5-FU by the sp ray drying method.
Colloid Surface A 2002; 6:269-279.
126.刘善奎,钟延强,王芳等.口蹄疫DNA疫苗海藻酸钠微球的制备及体外释放研究.药学服务与研究2004；4：107-111.
127. Maryellen S., David E., PaulaW.. Effect of p roteinmolecular weight on release from micron-sized PLGA microspheres. J. Control.Release 2001; 76:297-311.
128. Fwulong M., Shinshing S., Yimei L.. Chintin/PLGA blend microspheres as a biodegradable drug delivery system:a new delivery system for p rotein. Biomaterials 2003; 11:5023-5036.
129. Ywujang F., Shinshing S., Fuhu S.. Development of biodegradable copoly(lactic/glycolic acid) microspheres for the controlled release of 5-FU by the sp ray dryingmethod. Colloid Surface B 2002; 4:269-279.
130. Carrasguillo K.G., Stanley A.M., Aponte-Carro J.C.. Non-aqueous encap sulation of excip ient stabilizedsp ray-freeze dried BSA into poly(lactide-co-lycolide) microspheres results in release of native p rotein. J. Control. Release 2001; 3:199-208.
131.朱晓丽,顾相伶,张志国.单凝聚与复凝聚法制备昆虫激素十二醇微胶囊及其释放行为.高分子学报2007；5：491-494.
132.敦洁宁,邓树海,苗彩云.大蒜素壳聚糖微球的研究.山东大学学报：医学版2005；43：452-454.
133.刘利萍,李苹,吴泽志.5-FU壳聚糖／丝素复合磁微球的制备及体外性质研究.中国药学杂志2003；38：774-777.
134. Green B.K., Schleicher L., U.S. Pat.1956; 2,730:456-457.
135. Ranney M.W.. "Microencapsulation Technology", Noyes Development, ParkRidge, NJ,1969.
136. Gutchko M.H.. "Microcapsules and Microencapsulation Techniques", Noyes Data, Park Ridge, NJ,1976.
137. Yolles S., Leafe D.I., Meyer F.J.. Timed-release depot for anticancer agents.J. Pharm. Sci.1975; 64:115-116.
1. Qu X., Wirsen A., Albertsson A.C.. Novel pH-sensitive chitosan hydrogels: swelling behavior and states of water. Polymer 2000; 41:4589-4598.
2. Paula H.C.B., Gomes F.J.S., Paula R. C.M.. Swelling studies of chitosan/cashew nut gum physical gels.Carbohyd. Polym.2002; 48:313-318.
3. Alvarez-Lorenzo C., Concheiro A.. Reversible adsorption by a pH-and temperature-sensitive acrylic hydrogel. J. Control. Release 2002; 80:247-257.
4. Lubben I.M., Verhoef J.C., Borchard G., Junginger H.E.. Chitosan and its derivatives in mucosal drug and vaccine delivery. Eur. J. Pharm. Sci.2001; 14: 201-207.
5. Hejazi R., Amiji M.. Chitosan-based gastrointestinal delivery systems.J. Control. Release 2003; 89:151-165.
6. Prabaharan M., Mano J.F.. A novel pH and thermo-sensitive N,O-carboxymethyl. chitosan-graft-poly(N-isoproylacrylamide) hydrogel for controlled drug delivery e-Polymers,2007; 043:1-14.
7. El-Tahlawy K.F., El-Rafie S.M., Aly A.S.. Preparation and application of chitosan/poly(methacrylic acid) graft copolymer. Carbohyd. Polym.2006; 66: 176-183.
8. El-Tahlawy K., Hudson S.M.. Graft copolymerization of hydroxyethyl methacrylate onto chitosan. J. Appl. Polym. Sci.2001; 82:683-702.
9. Fu G.Q., Li H.Y., Yu H. F., Liu L., Yuan Z., He B.L.. Synthesis and lipoprotein sorption properties of porous chitosan beads grafted with poly(acrylic acid). React. Funct. Polym.2006; 66:239-246.
10. Fu G.Q., Zhao J.C., Yu H., Liu L., He B.L.. Bovine serum albumin-imprinted polymer gels prepared by graft copolymerization of acrylamide on chitosan. React. Funct. Polym.2007; 67:442-450.
11. Santos K.S.C.R.D., Coelho J.F.J., Ferreira P., Pinto I., Lorenzetti S.G., Ferreira E.I., Higa O.Z., Gil M.H.. Synthesis and characterization of membranes obtained by graft copolymerization of 2-hydroxyethyl methacrylate and acrylic acid onto chitosan. Int. J. Pharm.2006; 310:37-45.
12. Yazdani-Pedram M., Retuer J., Quijada R.. Hydrogels based on modified chitosan, 1 Synthesis and swelling behavior of poly(acrylic acid) grafted chitosan. Macromol Chem. Phys.2000; 201:923-930.
13. Jiang H.L., Kim Y.K., Arote R., Nah J.W., Cho M.H., Choi Y.J., Akaike T., Cho C.S.. Chitosan-graft-polyethylenimine as a gene carrier. J. Control. Release 2007; 117:273-280.
14. Yazdani-Pedram M., Retuert J.. Homogeneous grafting reaction of vinyl pyrrolidone onto chitosan. J. Appl. Polym. Sci.1997; 63:1321-1326.
15. Prabaharan M., Gong S.Q.. Novel thiolated carboxymethyl chitosan-g-b-cyclodextrin as mucoadhesive hydrophobic drug delivery carriers. Carbohyd. Polym.2008; 73:117-125.
16. Chen X.G., Wang Z., Liu W.S., Park H. J.. The effect of carboxymethyl-chitosan on proliferation and collagen secretion of normal and keloid skin fibroblasts. Biomaterials 2002; 23:4609-4614.
17. Li Z., Zhuang X.P., Liu X.F., Guan Y.L., Yao K.D.. Study on antibacterial O-carboxymethylated chitosan/cellulose blend film from LiCl/N,N-dimethylacetamide solution. Polymer 2002; 43:1541-1547.
18. El-Gendy E.H., Ali N.M., El-Shanshoury I.A.. Processes involved during radiation grafting of N-vinyl pyrrolidone onto poly(ethylene terephthatate) fabric. J. Appl. Polym. Sci.2006; 101:3009-3013.
19. Elassar A.A., El-Sawy N.M.. Recent developments in the radiation grafting of N-vinyl-2-pyrrolidone onto low-density polyethylene with cinnamonitrile derivatives. J. Appl. Polym. Sci.2005; 95:1189-1197.
20. Kim J.J., Park K.. Modulated insulin delivery from glucose-sensitive hydrogel dosage forms. J. Control. Release 2001; 77:39-47.
21. Berger J., Reist M., Mayer J. M., Felt O., Peppas N.A., Gurny R.. Structure and
interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications.Eur.J. Pharm. Biopharm.2004; 57:19-34.
22. Berger J., Reist M., Mayer J.M., Felt O., Gurny R.. Structure and interaction in chitosan hydrogels formed by complexation of aggregation for biomedical applications. Eur. J. Pharm. Biopharm.2004; 57:35-52.
23. Prabaharan M., Reis R.L., Mano J.F.. Carboxymethyl chitosan-graft-phosphatidylethanolamine:Amphiphilic matrices for controlled drug delivery. React. Funct. Polym.2007; 67:43-52.
24. Wheatley M.A., Chang M., Park E., Langer R.. Coated alginate microspheres: Factors influencing the controlled delivery of macromolecules. J. App.l Polym. Sci. 1991; 43:2123-2135.
25. Ma J.H., Zhang L., Fan B., Xu Y., Liang B.R.. A novel sodium carboxymethylcellulose/poly(N-isopropylacrylamide)/Clay semi-IPN nanocomposite hydrogel with improved response rate and mechanical properties J. Polym. Sc.i Part B:Polym. Phys.2008; 46:1546-1555.
26. Prabaharan M., Mano J. F.. Chitosan-graft-polyethylenimine as a gene carrier. Macromol. Biosci.2005; 5:965-973.
27. Lee C.F., Wen C.J., Chiu W.Y.. Synthesis of poly(chitosan-N-isopropylacrylamide) complex particles with the method of soapless dispersion polymerization. J. Polym. Sci. Part A:Polym. Chem.2003; 41: 2053-2063.
28. Qian F., Cui F.Y., Ding J.Y., Tang C., Yin C.H.. Chitosan graft copolymer nanoparticles for oral protein drug delivery:preparation and characterization. Biomacromolecules 2006; 7:2722-2727.
29. Mahdavinia G.R., Pourjavadi A., Hosseinzadeh H., Zohuriaan M.J.. Modified chitosan 4. Superabsorbent hydrogels from poly(acrylic acid-co-acrylamide) grafted chitosan with salt-and pH-responsiveness properties. Eur. Polym. J.2004; 40:1399-1407.
30. Isiklan N., Inal M., Yigitoglu M.. Synthesis and haracterization of poly(N-vinyl-2-pyrrolidone) grafted sodium alginate hydrogel beads for the controlled release of indomethacin. J. Appl. Polym. Sci.2008; 110:481-493.
31. Chauhan G.S., Singh B., Kumar S.. Synthesis and characterization of N-vinyl pyrrolidone and cellulosics based functional graft copolymers for use as metal ions and iodine sorbents. J. Appl. Polym. Sci.2005; 98:373-382.
32. Yazdani-Pedram M., Retuert J.. Homogeneous grafting reaction of vinyl pyrrolidone onto chitosan. J. Appl. Polym. Sci.1997; 63:1321-1326.
33. Wang Y.S., Liu L.R., Weng J., Zhang Q.Q.. Preparation and characterization of self-aggregated nanoparticles of cholesterol-modiwed O-carboxymethyl chitosan conjugates. Carbohyd. Polym.2007; 69:597-606.
34. Xie W.M., Xu P.X., Liu Q.. Antioxidant activity of water-soluble chitosan derivatives. Bioorg. Med. Chem. Lett.,2001; 11:1699-1701.
35. Chen S.L., Liu M.Z., Jin S.P., Chen Y.. Synthesis and swelling properties of pH sensitive hydrogels based on chitosan and poly(methacrylic acid) semi-interpenetrating polymer network. J. Appl. Polym. Sci.2005; 98:1720-1726.
36. Chen S.L., Liu M.Z., Jin S.P., Chen Y.. Structure and properties of the polyelectrolyte complex of chitosan with poly(methacrylic acid). Polym. Int.2007; 56:1305-1312.
37. Huang M.F., Jin X., Li Y.. Fang Y.E. Syntheses and characterization of novel pH-sensitive graft copolymers of maleoylchitosan and poly(acrylic acid). React. Funct. Polym.2006; 66:1041-1046.
38. Rokhade A.P., Patil S.A., Aminabhavi T.M.. Synthesis and characterization of semi-interpenetrating polymer network microspheres of acrylamide grafted dextran and chitosan for controlled release of acyclovir. Carbohyd. Polym.2007; 67:605-613.
39. Agnihotri S.A., Aminabhavi T.M.. Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine. Int. J. Pharm.2006; 324:103-115.
40. Kudaibergenov S.E., Sigitov V.B.. Swelling, shrinking, deformation, and oscillation of polyampholyte gels based on vinyl 2-aminoethyl ether and sodium acrylate. Langmuir 1999; 15:4230-4235.
41. Ritger P.L., Peppas N.A.. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices.J. Control. Release 1987; 5:37-42.
42. Peppas N.A., Bures P., Leobandung W., Ichikawa H.. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm.2000; 50:27-46.
43. Singh B., Chauhan G.S., Sharma D.K., Kant A., Gupta I., Chauhan N.. The release dynamics of model drugs from the psyllium and N-hydroxymethylacrylamide based hydrogels. Int. J. Pharm.2006; 325:15-25.
1. Yamada K., Furuya A., Akimoto M., Maki T., Suwa T., Ogata H.. Evaluation of gastrointestinal transit controlled-beagle dog as a suitable animal model for bioavailability testing of sustained-release acetaminophen dosage form. Int. J. Pharm.1995; 119:1-10.
2. Khan M.Z., Stedul H.P., Kurjakovic N.. A pH dependent colon-targeted oral drug delivery system using methacrylic acid copolymers. Ⅱ. Manipulation of drug release using Eudragit(?) L100 and Eudragit(?) S100 combinations. Drug Dev. Ind. Pharm.2000; 26:549-554.
3. Steed K.P., Hooper G., Monti N., Strolin Benedetti M., Fornasini G., Wilding I.R. The use of pharmacoscintigraphy to focus the development strategy for a novel 5-ASA colon targeting system ("TIME CLOCK"(?) system).J. Control. Release 1997; 49:115-122.
4. Hu Z.P., Kimura G., Mawatari S., Shimokawa T., Yoshikawa Y., Takada K.. New preparation method of intestinal pressure-controlled colon delivery capsules by coating machine and evaluation in beagle dogs. J. Control. Release 1998; 56: 293-302.
5. Fukui E., Miyamura N., Uemura K., Kobayashi M.. Preparation of enteric coated timed-release press-coated tablets and evaluation of their function by in vitro and in vivo tests for colon targeting. Int. J. Pharm.2000; 204:7-15.
6. Jeong Y.I., Ohno T., Hu Z., Yoshikawa Y., Shibata N., Nagata S., Takada K.. Evaluation of an intestinal pressure-controlled colon delivery capsules prepared by a dipping method. J. Control. Release 2001; 71:175-182.
7. Tozaki H., Komoike J., Tada C., Maruyama T., Terabe A., Suzuki T., Yamamoto A, Muranishi S.. Chitosan capsules for colon-specific drug delivery:improvement of insulin absorption from the rat colon. J. Pharm. Sci.1997; 86:1016-1021.
8. Kakoulides E.P., Smart J.D., Tsibouklis J.. Azocrosslinked poly(acrylic acid) for colonic delivery and adhesion specificity:synthesis and characterization.J. Control. Release 1998; 52:291-300.
9. Xu Y.M., Zhan C.Y., Fan L.H., Wang L., Zheng H.. Preparation of dual crosslinked alginate-chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system. Int. J. Pharm.2007; 336:329-337.
10. Ahrabi S.F., Madsen G., Dyrstad K., Sande S.A., Graffner C.. Development of pectin matrix tablets for colonic delivery of model drug ropivacaine. Eur. J. Pharm. Sci.2000; 10:43-52.
11. Semde R., Amighi K., Devleeschouwer M.J., Moes A.J.. Studies of pectin HM/Eudragit(?) RL/Eudragit(?) NE film-coating formulations intended for colonic drug delivery. Int. J. Pharm.2000; 197:181-192.
12. Ravi V., Siddaramaiah T. M.. Pramod Kumar. Influence of natural polymer coating on novel colon targeting drug delivery system. J. Mater. Sci:Mater. Med. 2008; 19:2131-2136.
13. Chen J., Liu M.Z., Jin S.P., Liu H.L.. Synthesis and characterization of k-carrageenan/poly(N,N-diethylacrylamide) semi-interpenetrating polymer network hydrogels with rapid response to temperature. Polym. Adv. Technol.2008; 19: 1656-1663.
14. Chen L.Y., Tian Z.G., Du Y.M.. Synthesis and pH sensitivity of carboxymethyl chitosan-based polyampholyte hydrogels for protein carrier matrices. Biomaterials 2004; 25:3725-3732.
15. Prabaharan M., Mano J.F.. Hydroxypropyl chitosan bearing b-cyclodextrin cavities:synthesis and slow release of its inclusion complex with a model hydrophobic drug. Macromol. Biosci.2005; 5:965-973.
16. Lin Y.W., Chen Q., Luo H.B.. Preparation and characterization of N-(2-carboxybenzyl)chitosan as a potential pH-sensitive hydrogel for drug delivery, Carbohyd. Res.2007; 342:87-95.
17. Lin Y.H., Liang H.F., Chung C.K., Chen M.C., Sung H.W.. Physically crosslinked alginate/N,O-carboxymethyl chitosan hydrogels with calcium for oral delivery of protein drugs. Biomaterials 2005; 26:2105-2113.
18. Panayiotou M., Pohner C., Vandevyver C., Wandrey C., Hilbrig F., Freitag R.. Synthesis and characterisation of thermo-responsive poly(N,N-diethylacrylamide) microgels. Reac. Funct Polyme.2007; 67:807-819.
19. Panayiotou M., Freitag R.. Synthesis and characterisation of stimuli-responsive poly(N,N'-diethylacrylamide) hydrogels. Polymer 2005; 46:615-621.
20. Shibanuma T., Aoki T., Sanui K., Ogata N., Kikuchi A., Sakurai V., Okano T.. Thermosensitive phase-separation behavior of poly(acrylic acid)-graft-poly(N,N-dimethylacrylamide) aqueous solution. Macromolecules 2000; 33:444-450.
21. Lee C.F., Wen C.J., Chiu W.Y.. Synthesis of Poly(chitosan-N-isopropylacrylamide) complex particles with the method of soapless dispersion polymerization. J. Polym. Sci. Part A:Polym. Chem.2003; 41: 2053-2063.
22. Qian F., Cui F.Y., Ding J.Y., Tang C., Yin C.H.. Chitosan graft copolymer nanoparticles for oral protein drug delivery:preparation and characterization. Biomacromolecules 2006; 7:2722-2727.
23. Brugnerotto J., Lizardi J., Goycoolea F.M., Arguelle-Monal W., Desbrieres J., Rinaudo M.. An infrared investigation in relation with chitin and chitosan characterization. Polymer 2001; 42:3569-3580.
24. Sarkyt E.K., Vladimir B.S.. Swelling, shrinking, deformation, and oscillation of polyampholyte gels based on vinyl N-aminoethyl ether and sodium acrylate. Langmuir 1999; 15:4230-4235.
25. Chen S.C., Wu Y.C., Mi F.L., Lin Y.H., Yu L.C., Sung H.W.. A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. J. Control. Release 2004; 96: 285-300.
26. Moura D.M.R., Guilherme M.R., Campese G.M.. Porous alginate-Ca2+hydrogels interpenetrated with PNIPAAm networks:Interrelationship between compressive stress and pore morphology. Eur. Polym. J.2005; 41:2845-2852.
27. Liu H.L., Liu M.Z., Jin S.P., Chen S.L.. Synthesis and characterization of fast responsive thermo-and pH-sensitive poly[(N,N-diethylacrylamide)-co-(acrylic acid)] hydrogels. Polym. Int.2008; 57:1165-1173.
28. Agnihotri S.A., Aminabhavi T.M.. Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine. Int. J. Pharm.2006; 324:103-115.
29. Zhang X.Z., Wu D.Q., Chu C.C.. Synthesis, characterization and controlled drug release of thermosensitive IPN-PNIPAAm hydrogels. Biomaterials 2004; 25: 3793-3805.
30. Ritger P.L., Peppas N.A.. A simple equation for description of solute release. II Fickian and anomalous release from swellable devices. J. Control. Release 1987; 5:37-42.
31. Peppas N.A., Bures P., Leobandung W., Ichikawa H.. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm.,2000; 50,27-46.
32. Tapia C., Corbalan V., Costa E., Gai M.N., Yazdani-Pedram M.. Study of the release mechanism of diltiazem hydrochloride from matrices based on chitosan-alginate and chitosan-carrageenan mixtures. Biomacromolecules 2005; 6: 2389-2395._
33. Chen S.L., Liu M.Z., Jin S.P., Wang B.. Preparation of ionic-crosslinked chitosan-based gel beads and effect of reaction conditions on drug release behaviors. Int. J. Pharm.2008; 349:180-187.
34. Nochos A., Douroumis D., Bouropoulos N.. In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads. Carbohyd. Polym.2008; 74: 451-457.
1. Chen X., Cui Z.C., Chen Z.M., Zhang K., Lu G., Zhang G., Yang B.. The synthesis and characterizations of monodisperse cross-linked polymer microspheres with carboxyl on the surface. Polymer 2002; 43:4147-4152.
2. Lee I.S., Cho M.S., Choi H.J.. Preparation of polyaniline coated poly(methyl methacrylate) microsphere by graft polymerization and its electrorheology. Polymer 2005; 46:1317-1321.
3. Kima J.W., Leeb J. E., Kima S.J., Leea J.S., Ryub J.H., Kima J., Hana S.H., Changa I.S., Suh K.D.. Synthesis of silver/polymer colloidal composites from surface-functional porous polymer microspheres. Polymer 2004; 45:4741-4747.
4. Kimura K., Kohama S., Yamashita Y., Uchida T., Sakaguchi Y.. Diameter control of poly(poxycinnamoyl) microspheres prepared by self-organizing polycondensation. Polymer 2003; 44:7383-7387.
5. Jones C.D., Lyon L.A.. Synthesis and characterization of multiresponsive core-shell microgels. Macromolecules 2000; 33:8301-8306.
6. Jones C.D., Lyon L.A.. Shell-restricted swelling and core Compression in poly(N-isopropylacrylamide) core-shell microgels. Macromolecules 2003; 36: 1988-1993.
7. Leobandung W., Ichikawa H., Fukumori Y., Peppas N.A.. Monodisperse nanoparticles of poly(ethylene glycol) macromers and N-isopropyl acrylamide for biomedical applications. J. Appl. Polym. Sci.2003; 87:1678-1684.
8.Ichikawa H., Fukumori Y.. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethyl cellulose matrix. J. Controlled Release 2000; 63:107-119.
9. Vihola H., Laukkanen A., Hirvonen J., Tenhu H.. B inding and release of drugs into and from thermosensitive poly(N-vinyl caprolactam) nanoparticles. Eur. J. Pharm. Sci.2002; 16:69-74.
10. Kawaguchi H., Fujimoto K.. Smart latexes for bioseparation. Bioseparation 1998; 7:253-258.
11. Panchapakesan B., DeVoe D.L, Widmaier M.R., Cavicchi R., Semancik S.. Nanoparticle engineering and control of tin oxide microstructures for chemical microsensor applications. Nanotechnology 2001; 12:336-349.
12. Bergbreiter D.E., Case B.L., Liu Y.S., Caraway J.W.. Poly(N-isopropylacrylamide) soluble polymer supports in catalysis and synthesis. Macromolecules 1998; 31: 6053-6062.
13. Guiseppi-Elie A., Sheppard N.F., Brahim S., Narinesingh D.. Enzyme microgels in packed-bed bioreactors with downstream amperometric detection using microfabricated interdigitated microsensor electrode arrays. Biotechnol. Bioeng. 2001; 75:475-484.
14. Irene B., Catherine D., Patrick C. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Delivery Rev.2002; 54:631-651.
15. Lee T.H., Wang J., Wang C.H.. Double-walled microspheres for the sustained release of a highly water soluble drug:characterization and irradiation studies. J. Control. Release 2002; 83:437-452.
16. Yang Y.Y., Shi M., Goh S.H., Moochhala S.M., Ng S., Heller J.. P OE/PLGA composite microspheres:formation and in vitro behavior of double walled microspheres. J. Control. Release 2003; 88:201-213.
17. Berkland C., Cox A., Kim K.K., Pack D.W.. Three-month, zero-order piroxicam release from monodispersed double-walled microspheres of controlled shell thickness. J. Biomed. Mater. Res.2004; 70A:576-584.
18. Marilia P., Ruth F.. Synthesis and characterisation of stimuli-responsive poly(N,N'-diethylacrylamide) hydrogels. Polymer 2005; 46:615-621.
19. Panayiotou M., Pohner C., Vandevyver C., Wandrey C., Hilbrig F., Freitag R.. Synthesis and characterisation of thermo-responsive poly(N,N-diethylacrylamide) microgels. Reac. Funct. Polym.2007; 67:807-819.
20. Wu X., Pelton R.H., Hamielec A.E., Woods D.R., McPhee W.. The kinetics of poly(N-isopropylacrylamide) microgel latex formation. Colloid Polym. Sci.1994; 272:467-477.
21. Antonietti M., Pakula T., Bremser W.. Rheology of small spherical polystyrene microgels:a direct proof for a new transport mechanism in bulk polymers besides reptation. Macromolecules 1995; 28:4227-4233.
22. Neyret S., Vincent B.. The properties of polympholyte microgel particles prepared by microemulsion polymerization. Polymer 1997; 38:6129-6134.
23.Ole Kiminta D.M., Luckham P.F., Lenon S.. The rheology of deformable and the responsive microgel particles. Polymer 1995; 36:4827-4831.
24. Wu C., Zhou S.Q.. Effects of surfactants on the phase transition of poly(N-isopropylacrylamide) in water. J. Polym. Sci. B:Polym. Phys.1996; 34: 1597-1604.
25. Chai Z.K., Zheng X., Sun X.F.. Preparation of polymer microspheres from solutions. J. Polym. Sci. B:Polym. Phys.2003; 41:159-165.
26. Xiao X.C., Chu L.Y. Chen W.M., Wang S., Xie R. Preparation of submicrometer-sized monodispersed thermoresponsive core-shell hydrogel microspheres. Langmuir 2004; 20:5247-5253.
27. Irene B., Catherine D., Patrick C.. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Delivery Rev.2002; 54:631-651.
28. Lee T.H., Wang J., Wang C.H.. Double-walled microspheres for the sustained release of a highly water soluble drug:characterization and irradiation studies. J. Control. Release 2002; 83:437-452.
29. Yang Y.Y., Shi M., Goh S.H., Moochhala S.M., Ng S., Heller J.. P OE/PLGA composite microspheres:formation and in vitro behavior of double walled microspheres. J. Control.dRelease 2003; 88:201-213.
30. Bergbreiter D.E., Case B.L., Liu Y.S., Caraway J.W.. Poly(N-isopropylacrylamide) soluble polymer supports in catalysis and synthesis. Macromolecules 1998; 31: 6053-6062.
31. Chen S.A.,Lee S.T.. Kinetics and mechanism of emulsifier-free emulsion polymerization:styrene/phydrophilic comonomer (acrylamid) system. Macromolecules 1991; 24:3340-3351.
32. Shibanuma T., Aoki T., Sanui K., Ogata N., Kikuchi A., Sakurai Y., Okano T.. Thermosensitive phase-separation behavior of poly(acrylic acid)-graft-poly(N,N-dimethylacrylamide) aqueous solution. Macromolecules 2000; 33:444-450.
33. Liu H.L., Liu M.Z., Jin S.P., Chen S.L.. Synthesis and characterization of fast responsive thermo-and pH-sensitive poly[(N,N-diethylacrylamide)-co-(acrylic acid)] hydrogels. Polym. Int.2008; 57:1165-1173.
34. Zhang X.Z., Zhuo R.X., Yang Y.Y.. Using mixed solvent to synthesize temperature sensitive poly(N-isopropylacrylamide) gel with rapid dynamics properties. Biomaterials 2002; 23:1313-1318.
35. Ritger P.L., Peppas N.A.. A simple equation for description of solute release. Ⅱ Fickian and anomalous release from swellable devices. J. Control. Release 1987; 5:37-42.
36. Gao C.M., Liu M.Z., Chen S.L., Jin S.P., Chen J.. Preparation of oxidized sodium alginate-graft-poly(2-dimethylamino ethyl methacrylate) gel beads and in vitro controlled release behavior of BSA. Int. J. Pharm.2009; 371:16-24.
1. Yoo H.S., Park T.G.. Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA-PEG block copolymer.J. Control. Release 2001; 70:63-70.
2. Shuai X.T., Ai H., Nasongkl N., Kim S., Gao J.M.. Micellar carriers based on block copolymers of poly(ε-caprolactone) and poly(ethylene glycol) for doxorubicin delivery. J. Control. Release 2004; 98:415-426.
3. Yu C.Y., Zhang X.C., Zhou F.Z., Zhang X.Z., Cheng S.X., Zhuo R.X.. Sustained release of antineoplastic drugs from chitosan-reinforced alginate microparticle drug delivery systems. Int. J. Pharm.2008; 357:15-21.
4. Jiang P., Bertone J.F., Colvin V.L.. A Lost-wax approach to monodisperse colloids and their crystals. Science 2001; 291:453-457.
5. Jin R., Cao Y., Mirkin C.A., Kelly K.L., Schatz G.C., Zheng J.G.. Photoinduced conversion of silver nanospheres to nanoprisms. Science 2001; 294:1901-1903.
6. Weda P., Trzebicka B., Dworak A., Tsvetanov C.B.. Thermosensitive nanospheres of low-density core-an approach to hollow nanoparticles. Polymer 2008; 49: 1467-1474.
7. Singh M.,Singh O.,Talwar G. P..Biodegradable Delivery System for a Birth Control Vaccine:Immunogenicity Studies in Rats and Monkeys. Pharm. Res.,1995; 12:1796-1800.
8. Bastos Gonzales D.,Ortega Vinuesa J. L., Nieves F. J.. Carboxylated latexes for covalent coupling antibodies, I. J. Colloid. Int. Sci.1995; 176:232-247.
9. Lee C. F.,Young T. H.,Huang Y. H.. Synthesis and properties of polymer latex with carboxylic acid functional groups for immunological studies. Polymer 2000; 41:8565-8571.
10. Kondo A.,Fukuda H.. Preparation of thermo-sensitive magnetic microspheres and their application to bioprocesses. Colloid and Surface A,1999;153:435-438.
11. Chen J.P.,Su D.R.. Modeling sludge as continuous mixture during thermal pyrolysis.J. Chin. Inst. Chem. Engrs.,2001; 32:241-251.
12. Santos R.M., Forcada J.. Acetal-functionalized polymer particles useful for immunoassays. J. Polym. Sci. A:Polym. Chem.,1997; 35:1605-1610.
13. Nardin C., Hirt T., Leukel J., Meier W.. Polymerized ABA triblock copolymer vesicles. Langmuir 2000; 16:1035-1041.
14. General S., Rudloff J., Thunemann A.F.. Hollow nanoparticles via stepwise complexation and selective decomplexation of poly(ethylene imine). Chem. Commun.2002; 5:534-535.
15. Gittins D.I., Caruso F.. Multilayered polymer nanocapsules derived from gold nanoparticle templates. Adv. Mater.2000; 12:1947-1949.
16. Jang J., Ha H.. Fabrication of hollow polystyrene nanospheres in microemulsion polymerization using triblock copolymers. Langmuir 2002; 18:5613-5618.
17. Tiarks F., Landfester K., Antonietti M.. Preparation of polymeric nanocapsules by miniemulsion polymerization. Langmuir 2001; 17:908-918.
18. Cheng C.J., Chu L.Y., Ren P.W., Zhang J., Hu L.. Preparation of monodisperse thermo-sensitive poly(N-isopropylacrylamide) hollow microcapsules. J. Colloid. Interface. Sci.2007; 313:383-388.
19. Lees-Haley P.R., Williams C.W.. Neurotoxicity of chronic low-dose exposure to organic solvents:A skeptical review. J. Clin. Psychol.1997;.5:699-712.
20. Yolles S., Leafe D.I., Meyer F.J.. Controlled release of biologically active compounds from bioerodible polymers. J. Pharm. Sci.,1975; 64:115-116.
21. Yu C.Y., Jia L.H., Yin B.C., Zhang X.Z., Cheng S.X., Zhuo R.X.. Fabrication of nanospheres and vesicles as drug carriers by self-assembly of alginate. J. Phys. Chem. C2008; 112:16774-16778.
22. Stops F., Fell J.T., Collett J.H.. Martini L.G.. Floating dosage forms to prolong gastro-retention-The characterisation of calcium alginate beads. Int. J. Pharm. 2008; 350:301-311.
23. Sarmento B., Ferreira D., Veiga F., Ribeiro A.. Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pre-gelation through DSC and FTIR studies. Carbohydr. Polym.2006; 66:1-7.
24. Sarmento B., Martins S., Ribeiro A., Veiga F., Neufeld R., Ferreira D.. Development and comparison of different nanoparticulate polyelectrolyte complexes as insulin carriers. Int. J. Pept. Res. Ther.2006;.12:131-138.
25. Cafaggi S., Russo E., Stefani R., Leardi R., Caviglioli G., Parodi B., Bignard G., De Totero D., Aiello C., Viale M.. Preparation and evaluation of nanoparticles made of chitosan or N-trimethyl chitosan and a cisplatin-alginate complex. J. Control. Release.2007; 121:110-123.
26. Shibanuma T., Aoki T., Sanui K., Ogata N., Kikuchi A., Sakurai V., Okano T.. Thermosensitive phase-separation behavior of poly(acrylic acid)-graft-poly(N,N-dimethylacrylamide) aqueous solution. Macromolecules 2000; 33:444-450.
27. Villa R., Folini M., Porta C.D., Valentini A., Pennati M., Daidone M.G., Zaffaronil N.. Inhibition of telomerase activity by geldanamycin and 17-allylamino,17-demethoxygeldanamycin in human melanoma cells. Carcinogenesis 2003; 24:851-859.
28. Lee C.F., Wen C.J., Chiu W.Y.. Synthesis of poly(chitosan-N-isopro-pylacrylamide) complex particles with the method of soapless dispersion polymerization. J. Polym. Sci. Part A:Polym. Chem.2003; 41:2053-2063.
29. Qian F., Cui F.Y., Ding J.Y., Tang C., Yin C.H.. Chitosan Graft Copolymer Nanoparticles for Oral Protein Drug Delivery:Preparation and Characterization. Biomacromolecules 2006; 7:2722-2727.
30. Ma L.W., Liu M.Z., Liu H.L., Chen J., Gao C.M., Cui D.P.. Dual crosslinked pH-and temperature-sensitive hydrogel beads for intestine-targeted controlled release. Polym. Adv. Technol.2010; 21:348-355.
31. Brugnerotto J., Lizardi J., Goycoolea F.M., Arguelle-Monal W., Desbrieres J., Rinaudo M.. An infrared investigation in relation with chitin and chitosan characterization. Polymer 2001; 42:3569-3580.
32. Colfen H., Antonietti M.. Crystal Design of Calcium Carbonate Microparticles Using Double-Hydrophilic Block Copolymers. Langmuir,1998; 14:582-589.
33. Colfen H., Qi L.. A Systematic Examination of the Morphogenesis of Calcium Carbonate in the Presence of a Double-Hydrophilic Block Copolymer.Chem. Eur. J.2001; 7:106-116.
34. Naka K., Tanaka Y., Chujo Y., Ito Y.. The effect of an anionic starburst dendrimer on the crystallization of CaCO3 in aqueous solution. Chem. Commun.,1999; 19: 1931-1932
35. Naka K, Tanaka Y, Chujo Y. Effect of Anionic Starburst Dendrimers on the Crystallization of CaCO3 in Aqueous Solution:Size Control of Spherical Vaterite Particles. Langmuir,2002; 18:3655-3658.
36. Quignard F. Cot D., Renzo F.D., Gerardin C. Core-shell copper hydroxide-polysaccharide composites with hierarchical macroporosity. Prog. Solid. State. Chem.2006; 34:161-169.
37. Zhang X.Z., Wu D.Q., Chu C.C.. Synthesis, characterization and controlled drug release of thermosensitive IPN-PNIPAAm hydrogels. Biomaterials 2004; 25: 3793-3805.
38. Marilia P., Ruth F.. Synthesis and characterisation of stimuli-responsive poly(N,N'-diethylacrylamide) hydrogels. Polymer 2005; 46:615-621.
39. Ma L.W., Liu M.Z., Chen J., Liu H.L., Cui D.P., Gao C.M.. Synthesis, characterization and drug release behavior of pH-responsive O-carboxymethyl chitosan-graft-poly(N-vinylpyrrolidone) hydrogel beads. Adv. Eng. Mater.2009; 11:B267-B274.
40. Ritger P.L., Peppas N.A.. A simple equation for description of solute release Ⅱ. Fickian and anomalous release from swellable devices. J. Control. Release.1987; 5:37-42.
41. Peppas N.A., Bures P., Leobandung W., Ichikawa H.. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm.2000; 50:27-46.
42. Tapia C., Corbalan V., Costa E., Gai M.N., Yazdani-Pedram M.. Study of the Release Mechanism of Diltiazem Hydrochloride from Matrices Based on Chitosan-Alginate and Chitosan-Carrageenan Mixtures. Biomacromolecules 2005; 6:2389-2395.
43. Singh B., Chauhan G.S., Sharma D.K., Kant A., Gupta I., Chauhan N.. The release dynamics of model drugs from the psyllium and N-hydroxymethylacrylamide based hydrogels. Int. J. Pharm.2006; 325:15-25.
1. Zhang L.F., Eisenberg A.. Multiple morphologies and characteristics of "crew-cut" micelle-like aggregates of polystyrene-b-poly(acrylic acid) diblock copolymers in aqueous solutions. J. Am. Chem. Soc.1996; 118:3168-3181.
2. Antonietti M., Forster S., Hartman J.. Novel amphiphilic block copolymers by polymer reactions and their use for solubilization of metal salts and metal colloids. Macromolecules 1996; 29:3800-3806.
3. Webber S.E.. Polymer micelles:an example of self-assembling polymers. J. Phys. Chem. B 1998; 102:2618-2626.
4. Yuan J.J., Li Y.S., Li S.Q.. Self-assembly of triblock copolymer PS-b-PEO-b-PS. Chem. J. Chin. Univ.2003; 24:371-373.
5. Moffitt M., Khougaz K., Eisenberg A.. Micellization of ionic block copolymers. Acc. Chem. Res.1996; 29:95-98.
6. Zhu H., Liu S.Y., Pan Q.M., Duan H.W. Jiang M.. Synthesis of amphiphilic block copolymer poly(styrene-b-acrylic acid) by atom transfer radical polymerization and its micellization. Chem. J. Chin. Univ.2002; 23:138-142.
7. Shen H.W., Eisenberg A.. Block length dependence of morphological phase diagrams of the ternary system of PS-b-PAA/dioxane/H2O.Macromolecules 2000; 33:2561-2572.
8. Bader H., Ringsdorf H., Schmidt B.. Watersoluble polymers in medicine. Angew. Makromol. Chem.1984; 123:457-485.
9. Liu J., Zeng F.. Allen C. In vivo fate of unimers and micelles of a poly (ethylene glycol)-block-poly(caprolactone) copolymer in mice following intravenous administration. Eur. J. Pharm. Biopharm.2007; 65:309-319.
10. Cgen Z., Wang Y., Feng Y.. Synthesis of hydroxyl-terminated copolymer of styrene and 4-vinylpyridine via nitroxide-mediated living radical polymerization. J. Appl. Polym. Sci.2004; 91:1842-1847.
11. Lee J.M., K. Lee, Min K.. The effect of polystyrene-block-poly(4-vinylpyridine) p repared by a RAFT method in the dispersion polymerization of styrene. Curr. Appl. Phys.2008; 8:732-735.
12. Luo X., Zhuang Y., Zhao X.. Controlled/living radical polymerization of styrene catalyzed by cobaltocene. Polymer 2008; 49:3457-3461.
13. Man H., Qiao X., Ming C.. Synthesis of amphiphilic block copolymer by atom transfer radical polymerization. J. South. Yangtze. Uni.2004; 3:79-82.
14. Samson A., Jenekhe X., Chen L.. Self-assembled aggregates of rodcoil block copolymers and their solubilization and encap sulation of fullerenes. Science 1998; 279:1903-1907.
15. Wang J.S., Matyjaszewski K.. Controlled/"living" radical polymerization. atom transfer radical polymerization in the presence of transition-metal complexes. J. Am. Chem. Soc.1995; 117:5614-5615.
16. Kato M., Kamigaito M., Sawamoto M., Higashimura T.. Polymerization of methyl methacrylate with the carbon tetrachloride/dichlorotris-(triphenylphosphine)ruthenium(Ⅱ)/Methylaluminum bis(2,6-di-tert-butylphenoxide) initiating system:possibility of living radical polymerization. Macromolecules 1995; 28:1721-1723.
17. Hua M., Yang W., Xue Q., Chen M.Q., Liu X.Y., Yang C.. Study on Synthesis of Amphiphilic PS-b-PMAA and Their Micellization. Acta. Chim. Sinica.2005,63, 63-67.
18. Wei L.H., Zhang W.C., Chen Y.. The Synthesis of amphophilic diblok copolymer PS-b-PAA and its morphology, nano-size aggregate formation in solutions. Acta Polym. Sin.2002; 4:548-551.
19. Cheng S.Y., Xu Z.S., Yuan J.J.. PS-b-PEO-b-PS triblock copolymers in aqueous micellization. Acta. Chim. Sinica.2000; 58:368-370.
20. Shibanuma T., Aoki T., Sanui K., Ogata N., Kikuchi A., Sakurai V., Okano T. Thermosensitive phase-separation behavior of poly(acrylic acid)-graft-poly(N,N-dimethylacrylamide) aqueous solution. Macromolecules 2000; 33:444-450.
21. Ma L.W., Liu M.Z., Liu H.L., Chen J., Cui D.P.. In vitro cytotoxicity and drug release properties of pH-and temperature-sensitive core-shell hydrogel microspheres. Inter. J. Pharm.2010; 385:86-91.
22. Ma L.W., Liu M.Z., Liu H.L., Chen J., Gao C.M., Cui D.P.. Dual crosslinked pH-and temperature-sensitive hydrogel beads for intestine-targeted controlled release. Polym. Adv. Tech.2010; 21:348-355.
23. Cao Z.Q., Liu W.G., Ye G.X., Zhao X.L., Lin X.Z., Gao P., Yao K. D.. N-isopropylacrylamide/2-hydroxyethyl methacrylate star diblock copolymers: synthesis and thermoresponsive behavior. Macromol. Chem. Phys.2006; 207: 2329-2335.
24. Badiger M.V., Rajamohanan P.R., Kulkarni M.G., Ganapathy S., Mashelkar R.A.. Proton MASS-NMR:a new tool to study thermoreversible transition in hydrogels. Macromolecules 1991; 24:106-111.
25. Nagasaki Y., Okada T., Scholz C., Iijima M., Kato M, Kataoka K.. The reactive polymeric micelle based on an aldehyde-ended poly(ethylene glycol)/poly(lactide) block copolymer. Macromolecules 1998; 31:1473-1479.
26. Weaver J.V.M., Bannister I., Robinson K.L., Bories-Azeau X., Armes S.P., Smallridge M., McKenna P.. Stimulus-responsive water-soluble polymers based on 2-hydroxyethyl methacrylate. Macromolecules 2004; 37:2395-2403.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |