基于端树枝化聚乙二醇的树枝化聚合物的合成与研究
|
摘要
树枝状大分子聚酯是至今为止唯一可降解的树枝状大分子,具有良好的生物相容性,低的细胞毒性,在药物载体、靶向控制释放以及组织工程领域具有广泛的应用前景。本文以聚乙二醇为中心,采用发散法合成了1-4代末端含有不同数量羟基的树枝化聚乙二醇大分子引发剂,并研究了基于此大分子引发剂的树枝化聚合物的合成及性质。研究主要分为以下三个方面：
(1)含有梳状聚己内酯(PCL)和线性聚乙二醇(PEG)的哑铃型三嵌段共聚物的合成与研究
以上述含有羟基的1-4代树枝化聚乙二醇为大分子为引发剂,引发己内酯开环聚合,合成了一种中间为亲水性的PEG链段,两端为32个疏水性的PCL链段的哑铃型三嵌段共聚物。共聚物中PCL链段聚合度可通过单体/引发剂比例加以调节。这种支化结构聚酯材料不仅能达到很高分子量和很窄的分子量分布,同时具有较好的亲水性,以及大量的活性端羟基可用于化学修饰。
(2)支化度和分子量对嵌段共聚物热性能、结晶性和亲水性的影响
为考察聚合物的支化度,分子量和聚合物的热性能,结晶性能之间的相互影响,合成了一系列具有相同分子量不同支化度,和一系列具有相同支化度不同分子量的聚合物,结果表明,在相同的分子量下,随支化度升高高,熔点降低,Tg则呈现先小幅升高后大幅降低的规律,结晶温度也向低温方向移动；在相同的支化度下,随分子量的增大,熔点、Tg以及结晶温度都向高温方向移动。
(3)载药微球的制备及体外释放研究
以第四代哑铃型三嵌段聚合物为壁材,分别采用乳液溶剂挥发法和复乳法制备了分别用于载紫杉醇和替莫唑胺的聚合物微球,考察了制备工艺对聚合物微球的外观形貌,尺寸和载药量的影响,并研究了载药微球在磷酸盐缓冲溶液(PBS)中的体外释放曲线,结果表明,两种载药微球都具有缓释效果,且释放时间大于15天。
Polyester dendrimers/dendrons with excellent biocompatibility is the one and only biodegradable dendrimer which has shown high potential in controlled drug delivery system and tissue engineerring. Divergent synthetic method has been applied in this study to synthesis the first-fourth generation macro-initiator polyethylene glycol terminated by polyester dendrons with different amounts of hydroxyl groups and the dendronized polymers based on these micro-initiators have also been investigated. The study has been divided into three parts:
(1) Synthesis and study of dumbbell-shaped tri-block copolymer consisting of polycaprolactone and poly(ethylene glycol)
A series of well-defined dumbbell-shaped tri-block copolymers consisting of comb-like polycaprolactone (PCL) and linear poly(ethylene glycol) (PEG) with narrow molecular weight distributions and varied PCL arm lengths have been synthesized via the sequential preparation of terminal dendronized polyhydric PEG and ring-opening polymerization of□-caprolactone (CL). The length of PCL arms can be readily controlled by the feed molar ratio of CL monomer to the hydroxyl groups in PEG macro-initiator.
(2) The influence of branching degree and molecule weight on the thermol properties、crystallization and biocompatibilities.
A series of copolymers with the same molecule weight and different branching degree and a series of copolymers with the same branching degree and different molecule weight were synthesized to evaluate the interrelationship of branching degree and molecule weight to thermol properties、crystallization and biocompatibilities of copolymers. And the results showed that the melting point and the crystallization temperature shifted to lower temperature with the increasing of branching degree when that series of copolymers had the same molecule weight, but the Tg of copolymers first increased within a narrow range and then decreased by a wide margin. When other series of copolymers had the same branching degree, the melting poin、Tg and crystallization temperature shifted to a higher temperature with the increasing of molecule weights of copolymers.
(3) The preparation of microspheres loading drug and the study of drug release in vitro.
The emulsion solvent evaporation method and the double emulsion solvent evaporation method were respectively used to prepare the copolymer microspheres loading paclitaxel and temozolomide based on the fourth generation dumbbell shaped tri-block copolymers. We evaluated the influence of preparation process of microspheres on the surface shape、size and entrapping drug amount of copolymers microspheres and studied the drug releasing curves of microspheres in PBS solution. The test results showed that both microspheres loading paclitaxel and temozolomide had the effect of controlled release and the controlled releasing time were higher than 15 days.
(1)含有梳状聚己内酯(PCL)和线性聚乙二醇(PEG)的哑铃型三嵌段共聚物的合成与研究
以上述含有羟基的1-4代树枝化聚乙二醇为大分子为引发剂,引发己内酯开环聚合,合成了一种中间为亲水性的PEG链段,两端为32个疏水性的PCL链段的哑铃型三嵌段共聚物。共聚物中PCL链段聚合度可通过单体/引发剂比例加以调节。这种支化结构聚酯材料不仅能达到很高分子量和很窄的分子量分布,同时具有较好的亲水性,以及大量的活性端羟基可用于化学修饰。
(2)支化度和分子量对嵌段共聚物热性能、结晶性和亲水性的影响
为考察聚合物的支化度,分子量和聚合物的热性能,结晶性能之间的相互影响,合成了一系列具有相同分子量不同支化度,和一系列具有相同支化度不同分子量的聚合物,结果表明,在相同的分子量下,随支化度升高高,熔点降低,Tg则呈现先小幅升高后大幅降低的规律,结晶温度也向低温方向移动；在相同的支化度下,随分子量的增大,熔点、Tg以及结晶温度都向高温方向移动。
(3)载药微球的制备及体外释放研究
以第四代哑铃型三嵌段聚合物为壁材,分别采用乳液溶剂挥发法和复乳法制备了分别用于载紫杉醇和替莫唑胺的聚合物微球,考察了制备工艺对聚合物微球的外观形貌,尺寸和载药量的影响,并研究了载药微球在磷酸盐缓冲溶液(PBS)中的体外释放曲线,结果表明,两种载药微球都具有缓释效果,且释放时间大于15天。
Polyester dendrimers/dendrons with excellent biocompatibility is the one and only biodegradable dendrimer which has shown high potential in controlled drug delivery system and tissue engineerring. Divergent synthetic method has been applied in this study to synthesis the first-fourth generation macro-initiator polyethylene glycol terminated by polyester dendrons with different amounts of hydroxyl groups and the dendronized polymers based on these micro-initiators have also been investigated. The study has been divided into three parts:
(1) Synthesis and study of dumbbell-shaped tri-block copolymer consisting of polycaprolactone and poly(ethylene glycol)
A series of well-defined dumbbell-shaped tri-block copolymers consisting of comb-like polycaprolactone (PCL) and linear poly(ethylene glycol) (PEG) with narrow molecular weight distributions and varied PCL arm lengths have been synthesized via the sequential preparation of terminal dendronized polyhydric PEG and ring-opening polymerization of□-caprolactone (CL). The length of PCL arms can be readily controlled by the feed molar ratio of CL monomer to the hydroxyl groups in PEG macro-initiator.
(2) The influence of branching degree and molecule weight on the thermol properties、crystallization and biocompatibilities.
A series of copolymers with the same molecule weight and different branching degree and a series of copolymers with the same branching degree and different molecule weight were synthesized to evaluate the interrelationship of branching degree and molecule weight to thermol properties、crystallization and biocompatibilities of copolymers. And the results showed that the melting point and the crystallization temperature shifted to lower temperature with the increasing of branching degree when that series of copolymers had the same molecule weight, but the Tg of copolymers first increased within a narrow range and then decreased by a wide margin. When other series of copolymers had the same branching degree, the melting poin、Tg and crystallization temperature shifted to a higher temperature with the increasing of molecule weights of copolymers.
(3) The preparation of microspheres loading drug and the study of drug release in vitro.
The emulsion solvent evaporation method and the double emulsion solvent evaporation method were respectively used to prepare the copolymer microspheres loading paclitaxel and temozolomide based on the fourth generation dumbbell shaped tri-block copolymers. We evaluated the influence of preparation process of microspheres on the surface shape、size and entrapping drug amount of copolymers microspheres and studied the drug releasing curves of microspheres in PBS solution. The test results showed that both microspheres loading paclitaxel and temozolomide had the effect of controlled release and the controlled releasing time were higher than 15 days.
引文
[1]Buhleier E, Wehner W and Vogtle F, "Cascade and Nonskid-chain-like Synthesis of Molecular Cavity Topologies", Synthesis,2,155-158,1978.
[2]Tomalia D.A, Baker H, Dewald J, Hall M, Kallos G, Martin S, Roeck J, Ryder J and Smith P, "A New Class of Polymers:Starburst-Dendritic Macromolecules", Polym. J., 17(1),117-132,1985.
[3]Newkome G.R, Yao Z.Q, Baker G.R and Gupta V.K, "Cascade molecules:A new approach to micelles, A", J. Org. Chem.,50(11),2003-2006,1985.
[4]Pushkar S, Philip A, Pathak K and Pathak D, "Dendrimers:Nanotechnology Derived Novel Polymers in Drug Delivery", Indian J. Pharm. Educ. Res.,40 (3),153-158,2006.
[5]Sakthivel T and Florence A.T, "Adsorption of Amphipathic Dendrons on Polystyrene Nanoparticles", Int. J. Pharm.,254,23-26,2003.
[6]Yiyun C, Zhenhua X, Minglu M and Tonguen X, "Dendrimers as Drug Carriers: Applications in Different Routes of Drug", J.Pharma.Sci.,97(1),123-143,2008.
[7]Hawker C and Frechet J.M.J, "A new convergent approach to monodisperse dendritic molecule" J. Chem. Soc. Chem. Commun,15,1010-1012,1990.
[8]Hawker C, Wooley K.L and Frechet J.M.J, J.Chem. Soc. Perkin. Trans.,1,1287-1289, 1993.
[9]Frechet J.M.J and Tomalia D.A, "Introduction to the Dendritic state", Dendrimers and other Dendritic Polymers, John Wiley & Sons Ltd,24-23,2001.
[10]Sonke S and Tomalia D.A, "Dendrimers in biomedical applications reflections on the Field", Advanced Drug Delivery Reviews,57,2106-2129,2005.
[11]Christine D, Ijeoma F.U and Andreas GS, "Dendrimers in gene delivery", Advanced Drug Delivery Reviews,57,2177-2202,2005.
[12]Freeman A.W and Frechet J.M.J, "Developments in the Accelerated Convergent Synthesis of Dendrimers", Dendrimers and other Dendritic Polymers Edited by Jean M. J. Fre'chet and Donald A. Tomalia,91-101.
[13]Barbara K. and Maria B., "Review Dendrimers:properties and applications", Acta Biochimica Polonica,48 (1),199-208,2001.
[14]R.P.Patel et al. "Dendrimers:A new innovation in drug delivery", Pharma Bio World, 42-52,2007.
[15]Boris D, Rubinstein M, "A self-consistent mean field model of a starburst dendrimer: dense core vs. dense shell", Macromolecules,29,7251-7260,1996.
[16]Chai M, Niu Y., Youngs W.J and Rinaldi P.L, "Structure and conformation of DAB dendrimers in solution via multidimensional NMR techniques", J. Am. Chem. Soc., 123,4670-4678,2001.
[17]Gupta U, Agashe H and Jain N.K, "Polypropylene imine dendrimer mediated solubility enhancement:effect of pH and functional groups of hydrophobes", J. Pharm. Sci.,10(3), 358-67,2007.
[18]Wang D.J and Imae T, "fluorescence emission from Dendrimer & its pH dependence", J. Am. Chem. Soc.,126(41),13204-13205,2004.
[19]Zinselmeyer B.H, Mackay S.P, Schatzlein A.G and Uchegbu I.F, "The lower-generation polypropylenimine dendrimers are effective gene-transfer agents", Pharm. Res.,19,960-967, 2002.
[20]Jevprasesphant R, Penny J, Jalal R, Attwood D, McKeown N.B and D'Emanuele A. "The influence of surface modification on the cytotoxicity of PAMAM dendrimers", Int. J. Pharm.,252,263-266,2003.
[21]Jevprasesphant R, Penny J, Jalal R, Attwood D, McKeown N.B and D'Emanuele A., "Engineering of dendrimer surfaces to enhance transepithelial transport and reduce cytotoxicity", Pharm. Res.20,1543-1550,2003.
[22]Satija J, Gupta U and Jain N.K "Pharmaceutical and biomedical potential of surface engineered dendrimers" Crit Rev Ther Drug Carrier Syst.,24 (3),257-306,2007.
[23]Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, Weener J.W, Meijer E.W, Paulus W and Duncan R, "Dendrimers:relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of I-125-labelled polyamidoamine dendrimers in vivo", J.Control. Release,65,133-148,2000.
[24]Uchegbu I.F, Sadiq L, Pardakhty A, El-Hammadi M, Gray A.I, Tetley L, Wang W, Zinselmeyer B.H and Schatzlein A.G, "Gene transfer with three amphiphilic glycol chitosans —the degree of polymerisation is the main controller of transfection efficiency", J. Drug Target.,12,527-539,2004.
[25]Brownlie A, Uchegbu I.F and Schatzlein A.G, "PEI-based vesicle-polymer hybrid gene delivery system with improved biocompatibility", Int. J. Pharm.,274,41-52,2004.
[26]Schatzlein A.G, Zinselmeyer B.H, Elouzi A, Dufes C, Chim Y.T, Roberts C.J, Davies M.C, Munro A, Gray A.I and Uchegbu I.F, "Preferential liver gene expression with polypropylenimine dendrimers", J. Control. Release,101,247-258,2005.
[27]Chen H.T, Neerman M.F, Parrish A.R and Simanek E.E, "Cytotoxicity, hemolysis, and acute in vivo toxicity of dendrimers based on melamine, candidate vehicles for drug delivery", J. Am. Chem. Soc.,126,10044-10048,2004.
[28]Gillies E.R. and Frechet J.M.J, "Dendrimers and dendritic polymers in drug delivery" Drug Discovery Today,10,35-43,2005.
[29]Esfand, R. and Tomalia, D.A. "Polyamidoamine (PAMAM) dendrimers:from biomimicry to drug delivery and biomedical applications". Drug Discov. Today,6,427-436, 2001.
[30]Jevpraesesphant, R. et al., "The influence of surface modification on the cytotoxicity of PAMAM dendrimers", Int.J. Pharm.,252,263-266,2003.
[31]Hawker, C.J. and Frechet, J.M.J. "Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules". J. Am.Chem. Soc.,112,7638-7647,1990.
[32]Liu, M. et al. "Water-soluble unimolecular micelles:their potential as drug delivery agents". J. Control. Release,65,121-131,2000.
[33]Liu, M. et al. "Water-soluble dendrimer-polyethylene glycol starlike conjugates as potential drug carriers". J. Polym. Sc i., A 37,3492-3503,1999.
[34]Haag, R. et al. "An approach to glycerol dendrimers and pseudo-dendritic polyglycerols" J. Am. Chem. Soc.,122,2954-2955,2000.
[35]Neerman M.F et al. "In vitro and in vivo evaluation of a melamine dendrimer as a vehicle for drug delivery". Int. J. Pharm.,281,129-132,2004.
[36]Caminade A.M, Laurent R. and Majoral J.P, "Characterization of dendrimers", Advanced Drug Delivery Reviews,57,2130-2146,2005.
[37]Mohammad N and Antony D, "Crossing cellular barriers using dendrimer nanotechnologies", Current Opinion in Pharmacology,6,522-527,2006.
[38]Lee S.C "Dendrimers In Nanobiological Devices", Dendrimers and other Dendritic Polymers Edited by Fre'chet J.M.J and Tomalia D.A.,547-554.
[39]Kleij A.W, Ford A, JastrzebskI H and Vankoten G, "Dendritic Polymer Applications: Catalysts", Edited by Fre'chet J.M.J and Tomalia D.A.,485-507.
[40]Kofoed J and Reymond J, "Dendrimers as artificial enzymes", Current Opinion in Chemical Biology,9,656-664,2005.
[51]N.K.Jain, Controlled and Novel drug delivery,04 Edition,236-237,21.
[52]S.P.Vyas and R.K.Khar, Targeted and Controlleddrug delivery,07 Edition,418.
[53]Kreuter J., Nefzger M., Liehl E., CzokR. andVoges R. (1983) J.Pharm sci.72,1146.
[54]Margel S. and Wiesel E. (1984) J.polym.sci.22,145.
[55]Wakiyama N., Juni K. and Nakano M.(1981)chem..pharm.Bull.29,3363.
[56]Sugibayashi K., Akimoto M., Moromoto Y.,Nadai T. and Kato Y.(1979) pharmacobiodyn.23,50.
[57]Yoshioka T., Hashida M., Muranishi S. andSezakiH. (1981) Int.J.pharm.8,131.
[58]Russel G.F. (1983) pharma.Int.4,260.
[59]Woodland J.H.R., Yolles S., Blake D.A., HetrichM.and Meyer F.J.(1973) J. Med.chem.16,897.
[60]Rojas J., Pinto. Alphandary H., LeoE., Pecqests.,couvreur P., Gulik A. and Fattal. E. (1999)Pharm Res.16,255.
[61]Albertson AC., Carlfors J. and Sturess on C.(1993) J. Appl.polym.Sci.62,695.
[62]Renbaum A. (1983) US patent 4,413,070.
[63]S.P.Vyas & R.K.Khar, Targeted & Controlleddrug delivery.2007 Edition,435.
[64]KoffUS patent (March21963) 3,080,292.
[65]John P.M and Becker. C.H. (1968) J.pharm.sci.57,584.
[66]Schugens C., Larvelle. N., Nihantn., GrandfilsC., Jerome R. and Teyssie. P. (1994) J.Control.Rel.32,161.
[67]Mathews B.R. and Nixon J.R.(1974)J.pharmPharmacrol.26,283.
[68]N.K.Jain, Advances in controlled & Novel drugdelivery,03 Edition,71.
[69]Venkatesh H. (1989) "A buccal delivery systemof Salbutamol Sulphate" M.Pharm; Budrinarayan, N. (1991) "Utilisation andEvaluation of plant products in pharmaceutical formulations".M.Pharm.
70] Tanaka, W; Akito, E; Yoshida, K.; Terada, T.andNinomiya, H. (1977) "pharmaceutical preparations for oral cavity administration" USpatent No.4059686.
[71]Ishida, M; Nambu, N.and Nagai, T. (1983a)"Highly viscous gel ointment containing carbapol for application to the oral mucosa".Chem..pharm Bull.,31:4561.
[72]Collins, A.E and Deasy, P.B (1990)"Bioadhesive lozenge for the improved delivery of cetypyridinium chloride".J.pharm.sci.,79(2):116-120.
[73]Save T. and Venkatachalam P. (1994)"Bioadhesive tablets of Nifedipine: Standardization of a novel buccoadhesiveerodible carrier". Drug Dev.Ind. pharm.,20(19): 3005-3014.
[74]Dev rajan,P.V;Gupta S.; Gandhi A.S.;Niphadkar,P.V. and Shah.(1999)"Trans mucosal drug delivery systems ofSalbutamol Sulfate." 26th Int.Symp. Control.Rel.Bioact.Mater.,650.
[75]Lopez, C.R; Portero, A.; Vila-Jato, J.C. andAlonso, M.J. (1998) "Design and Evaluation ofChitosan/Ethylcellulose mucoadhesive bilayered devices for buccal drug delivery."J.control.Rel.,55:143-152.
[76]Parodi, B.; Russo, E.; Caviglioli, G.; Cafaggi, S.and Binardi, G. (1996) "Development &characterization of a buccoadhesive dosage from of Oxydodone hydrochloride". Drug Dev.Ind.pharm.,22(5):445-450.
[77]Chien, Y.W.; Corbo, D.C. and Liv, J.C. (1991) "Mucosal delivery of progestational Steroids from a Controlled release device:in vitro/in vivo relationship."DrugDev.Ind.pharm.,17(17):2269-2290.
[78]Cassidy, J.P.; Landcert, N.M.and Quardos, E. (1993) "controlled buccal delivery of buprenorphine". J.control.Rel.,25:21-29.
[79]Dortune, B.; Ozer, L.and Vyanik, N.(1998) "Development and invitro Evaluation of buccoadhesive pindodlo tablet formulation." Drug Dev.Ind.pharm.,24(3):281-288.
[80]Guo, J.H. (1994) "Bioadhesive polymer buccal patches for buprenorphine controlled delivery:formulation in vitro adhesive and release properties". Drug Dev.Ind.pharm., 20(3):315-325.
[81]Nagai, T.; Machida, Y.; Suzuki Y.and Ikura, H. (1980) "Method & preparation for administration to the mucosa & preparation for administration to the mucosa of the oral or nasal cavity" US patent NO.4226848.
[82]Chein, YW.and Novir, M. (1996) "Mucosal adhesive device for long acting delivery of pharmaceutical combinations in oral cavity". US patent NO.5578315.
[83]Fabregas, J.L.and Garcia, N. (1995) "Invitro studies on buccoadhesive tablet formulations of hydro cortisone hemisuccinate". Drug Dev.Ind.pharm.,21(14):1689-1696.
[84]Rathbone, M.J.; Purve, R.:Ghazati, F.A.and HO, P.C. (1996) "In vivo techniques for studying the oral mucosa absorption characteristics of drugs in animals and humans." In Rathbone, M.J. (ed.), oral mucosal delivery systems, Marcel Dekker Inc.Newyork.,121-156.
[85]Lu, M.F.and Hui, H.W. (1996) "Delivery of rennin inhibitors through mouth mucosa" Drug Dev.Ind.pharm.,22 (11); 1167-1171.
[86]Yukimatsu, K.; Nozaki, Y.; Kakumoto, M.and Ohta, M. (1994) "Development of a transmucosal controlled release device for systemic delivery of antianginal drug sphar maco kinetics and pharmacodynamics". Drug Dev.Ind.pharm,20(4):503-534.
[87]Hussain, M.A; Aungst, B.J.; Kearney A. and Shefter, E. (1987) "Buccal and oral bioavailability of naloxone and naltrexone in rats". INT, J.pharm.,36:127.
[88]Oh, C.K. and Ritschel., W.A. (1999a) "Biopharmaceutical aspects of buccal absorption of insulin rabbits I. Effects of dose, size, Ph & sorption enhancers:in vivo in vitro correlation". Pharm.Res.,5-5-100.
[89]Oh, C.K. and Ritschel, W.A. (1988b) "Biopharmaceutical aspects of buccal absorption of insulin in rabbits II. Absorption characteristics of insulin through the buccal mucosa". pharma.Res.,5-5-100.
[90]Kellaway, I.W. and warren, S.I. (1991) "Mucoadhesive hydrogels". Proc.Intern.symp.Control.Rel.Bioact.Mater.,18:73.
[91]Ishida, M.:Nambu, N.and Nagai, T.(1983a) "Highly viscous gel ointment containing carbopol for application to the oral mucosa".Chem.pharm.Bull.,31:4561.
[92]Ishida, M.; Nambu, N. and Nagai, T. (1983b) "Ointment type oral mucosal dosage form of carbopol containing prednisolone for the treatment of aphtha". Chem.pharm.Bull.,31:1010.
[93]Hoogstrate, A.J., verhoef, J.C.; Tuk., B.;Pijpers, A.; Vercheijden,J.H.M.; Jungiger, H.E. andBodde, H.C. (1996b) "Invivo buccal delivery of fluorescein iso thiocyanate-dextran 4 457-460.
[94]Burnside, B.A; Keith, A.P. and snipes, W.(1989) "micro porous hollow fibers as a peptide delivery system via the bucca activity ".proceed.inter.symp.control. Rel.Bioact. mater.,16:94.
[95]Rathone, M.J. (1991a) "Human buccal absorption I.A method for Estimating the transfer kinetics of drugs W cross the human buccal membrane". Int.J.pharm.,69:103.
[96]N.Venkateswarlu, Biopharmaceutics and kinetics,2004 Edition,53,54.
[97]Widder K.J., Sanyci A.E., Ovadia H., and Paterson P.Q. (1979) Clin. Immuno. Immuno pathol.14.395.
[98]Funden berg H.H., Stites D.P., Caldwel J.L.and Wells J.V. (1978) In:Basic and clinical immunology,2 ed., Lange Medical, Los Altosca.
[99]Capron A.C., Locht C. and Fracchia G.N (1994) Vaccine.12,667; Edelman R. (1993) vaccine 11,1361; Drews J. (1984) Immunostimulantien, Klin. Wochenscher.62,254; Spier K.E. (1993) vaccine 11,1450.
[100]Nachts S. and Martin K. (1990) In:The microsponges a novel topical programmable delivery formulation, Marcel Dekker Inc., Newyork.,299.
[1]Gillies E. R., Edward D, Frchet J. M. J., Szoka F. C. Biological E valuation of Polyester Dendrimer:Poly(ethylene oxide) "Bow-Tie" Hybrids with Tunable Molecular Weight and Architecture. Mol Pharm.2005,2 (2):129-138
[2]Daniel W, Salah-Eddine S, Andholger F. Hyperbranched Polyglycerols:From the Controlled Synthesis of Biocompatible Polyether Polyols to Multipurpose Applications. Accounts of Chemical Rearch.2010,43 (1):129-141
[3]Zhang X.L, Hyperbranched aromatic polyesters:From synthesis to applications. Progress in Organic Coatings 2010,69:295-309
[4]Lu Tian, Paula T. Hammond. Comb-Dendritic Block Copolymers as Tree-Shaped Macromolecular Amphiphiles for Nanoparticle Self-Assembly. Chem Mater.2006,18 (17):3976-3984
[5]Henrik Ihre, Omayra L. Padilla De Jesus, Jean MJ Frechet. Fast and Convenient Divergent Synthesis of Aliphatic Ester Dendrimers by Anhydride Coupling. J Am Chem Soc.2001, 123:5908-5917
[1]Yang Y, Bajaj N, Xu PS, Ohn K, Tsifansky MD, Yeo Y. Development of highly porous large PLGA microparticles for pulmonary drug delivery. Biomaterials.2009,30(10): 1947-1953
[2]Nasongkla N, Shuai X, Ai H, Brent DW, John P, David AB, Gao J. cRGD-Functionalized Polymer Micelles for Targeted Doxorubicin Delivery. Angew Chem Int Ed.2004.43: 6323-6327
[3]Ouchi T, Toyohara M, Arimura H, Ohya Y Preparation of Poly(L-lactide)-Based Microspheres Having a Cationic or Anionic Surface Using Biodegradable Surfactants. Biomacromolecules.2002,3:885-888
[4]Deng C, Tian HY, Zhang PB, Sun J, Chen XS, Jing XB. Synthesis and Characterization of RGD Peptide Grafted Poly(ethylene glycol)-b-Poly(L-lactide)-b-Poly(L-glutamic acid) Triblock Copolymer. Biomacromolecules.2006,7:590-596
[5]Li SM, Garreau H, Pauvert B, McGrath J, Toniolo A, Vert M. Enzymatic Degradation of Block Copolymers Prepared from ε-Caprolactone and Poly(ethylene glycol). Biomacromolecules.2002,3:525-530
[6]Kwon GS, Kataoka K. Block copolymer micelles as long-circulating drug vehicles. Adv Drug Delivery Rev.1995,16:295-309.
[7]Li SM, Liu LJ, Garreau H, Vert M. Lipase-Catalyzed Biodegradation of Poly(ε-caprolactone) Blended with Various Polylactide-Based Polymers. Biomacromolecules.2003,4:372-377.
[8]Tabata Y. The importance of drug delivery systems in tissue engineering. Pharm Sci Technol Today.2000,3:80-89
[9]Sheridan MH, Shea LD, Peters MC, Mooney DJ. Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery. J Control Release.2000, 64:91-102
[10]Baldwin SP, Saltzman WM. Materials for protein delivery in tissue engineering. Adv Drug Delivery Rev.1998,33:71-86
[11]Whang KM, Goldstick TK, Healy KE. A biodegradable polymer scaffold for delivery of osteotropic factors. Biomaterials.2000,21:2545-2551
[12]Breitenbath A, Kissel T. Biodegradable comb polyesters Part 1 synthesis, characterization and structural analysis of poly(lactide) and poly(lactide-coglycolide) grafted onto water-soluble poly(vinyl alcohol) as backbone. Polymer.1998,39:3261-3271
[13]Luo YF, Wang YL, Niu XF, Shang JF. Evaluation of the cytocompatibility of butanediamine- and RGDS-grafted poly(dl-lactic acid). Eur Polym J.2008,44: 1390-1402
[14]Zhao YL, Cai Q, Jiang J, Shuai XT, Bei JZ, Chen CF, Xi F. Synthesis and thermal properties of novel star-shaped poly(L-lactide)s with starburst PAMAM-OH dendrimer macroinitiator. Polymer.2002,43:5819-5825
[15]Li YX, Volland C, Kissel T. Biodegradable brush-like graft polymers from poly(D，L-lactide) or poly(D,L-lactide-coglycolide) and charge-modified, hydrophilic dextrans as backbone—in-vitro degradation and controlled releases of hydrophilic macromolecules. Polymer.1998,39:3087-3097
[16]Breitenbach A, Pistel KF, Kissel T. Biodegradable comb polyesters. Part Ⅱ. Erosion and release properties of poly(vinyl alcohol)-g-poly(lactic-co-glycolic acid). Polymer.2000, 41:4781-4792
[17]Cai Q, Zhao YL, Bei JZ, Xi F, Wang SG. Synthesis and Properties of Star-Shaped Polylactide Attached to Poly(Amidoamine) Dendrimer. Biomacromolecules.2003,4, 828-834
[18]Chen HT, Neerman MF, Parrish AR, Simanek EE. Cytotoxicity, Hemolysis, and Acute in Vivo Toxicity of Dendrimers Based on Melamine, Candidate Vehicles for Drug Delivery. J Am Chem Soc.2004,126:10044-10048
[19]Okuda T, Kawakami S, Akimoto N, Niidome T, Yamashita F, Hashida M. J Control Release.2006,116:330-336
[20]Okuda T, Kawakami S, Maeie T, Niidome T, Yamashita F, Hashida M. PEGylated lysine dendrimers for tumor-selective targeting after intravenous injection in tumor-bearing mice. J Control Release.2006,114:69-77
[21]Gillies ER, Dy E, Frechet JMJ, Szoka FC. Biological Evaluation of Polyester Dendrimer:Poly(ethylene oxide) "Bow-Tie" Hybrids with Tunable Molecular Weight and Architecture. Mol Pharmaceut.2005,2:129-138
[22]Gillies ER, Frechet JMJ. Designing Macromolecules for Therapeutic Applications:Polyester Dendrimer-Poly(ethylene oxide) "Bow-Tie" Hybrids with Tunable Molecular Weight and Architecture. J Am Chem Soc.2002,124:14137-14146
[23]Guillaudeu SJ, Fox ME, Haidar YM, Dy EE, Szoka FC, Frechet JMJ. PEGylated Dendrimers with Core Functionality for Biological Applications. Bioconjuag Chem. 2008,19:461-469
[24]Cai Q, Wan YQ, Bei JZ, Wang SG. Synthesis and characterization of biodegradable polylactide-grafted dextran and its application as compatilizer. Biomaterials.2003,24: 3555-3562
[25]Finne A, Albertsson AC. Controlled Synthesis of Star-Shaped L-Lactide Polymers Using New Spirocyclic Tin Initiators. Biomacromolecules.2002,3:684-490
[26]Kricheldorf HR, Hachmann TH, Schwarz G. Telechelic and Star-Shaped Poly (L-lactide)s by Means of Bismuth(III) Acetate as Initiator. Biomacromolecules.2004,5: 492-496
[27]Ydens I, Degee P, Dubois P, Libiszowski J, Duda A, Penczek S. Combining ATRP of Methacrylates and ROP of L,L-Dilactide and ε-Caprolactone Macromolecular Chemistry and Physics. Macromol Chem Phys.2003,204:171-179
[28]Teramoto Y, Nishio Y. Cellulose diacetate-graft-poly(lactic acid)s:synthesis of wide-ranging compositions and their thermal and mechanical properties. Polymer.2003, 44:2701-2709
[29]Nouvel C, Dubois P, Dellacherie E, Six JL. Controlled synthesis of amphiphilic biodegradable polylactide-grafted dextran copolymers. J Polym Sci Part A:Polym Chem. 2004,42:2577-2588
[30]Du YJ, Lemstra PJ, Nijenhuis AJ, Van Aert HAM, Bastiaansen C. ABA Type Copolymers of Lactide with Poly (ethylene glycol). Kinetic, Mechanistic, and Model Studies. Macromolecules.1995,28:2124-2132
[31]Yang JL, Zhao T, Zhou YC, Liu LJ, Li G, Zhou EL, Chen XS. Single Crystals of the Poly(1-lactide) Block and the Poly(ethylene glycol) Block in Poly(1-lactide)-poly(ethylene glycol) Diblock Copolymer. Macromolecules.2007,40:2791-2797
[32]Yasugi KJ, Nakamura T, Nagasaki Y, Kato M, Kataoka K. Sugar-Installed Polymer Micelles:Synthesis and Micellization of Poly(ethylene glycol)-Poly(D,L-lactide) Block Copolymers Having Sugar Groups at the PEG Chain End. Macromolecules.1999,32: 8024-8032
[33]Han DK, Hubbell JA. Synthesis of Polymer Network Scaffolds from L-Lactide and Poly(ethylene glycol) and Their Interaction with Cells. Macromolecules.1997,30: 6077-6083
[34]Schindler A, Hibionada YM, Pitt CG. Aliphatic polyesters. Ⅲ. Molecular weight and molecular weight distribution in alcohol-initiated polymerizations of ε-caprolactone. J Polym Sci Part A:Polym Chem.1982,20:319-326
[35]Zhang XC, MacDonald DA, Mattheus FA, McAuley GKB. Mechanism of lactide polymerization in the presence of stannous octoate:The effect of hydroxy and carboxylic acid substances. J Polym Sci Part A:Polym Chem.1994,32:2965-2970
[36]Nijenhuis AJ, Grijpma DW, Pennings AJ. Lewis acid catalyzed polymerization of L-lactide. Kinetics and mechanism of the bulk polymerization. Macromolecules.1992, 25:6419-6424
[37]Ryner M, Stridsberg K, Albertsson AC, Von Schenck H, Svensson M. Mechanism of Ring-Opening Polymerization of 1,5-Dioxepan-2-one and L-lactide with Stannous 2-Ethylhexanoate. A Theoretical Study. Macromolecules.2001,34:3877-3881
[38]Kowalski A, Duda A, Penczek S. Mechanism of Cyclic Ester Polymerization Initiated with Tin (Ⅱ) Octoate.2. Macromolecules Fitted with Tin (Ⅱ) Alkoxide Species Observed Directly in MALDI-TOF Spectra. Macromolecules.2000,33:689-695
[39]Gottschalk G, Frey H. Hyperbranched Polylactide Copolymers. Macromolecules.2006, 39:1719-1723
[40]Numata K, Srivastava RK, Finne WA, Albertsson AC, Doi Y, Abe H. Branched Poly(lactide) Synthesized by Enzymatic Polymerization:Effects of Molecular Branches and Stereochemistry on Enzymatic Degradation and Alkaline Hydrolysis. Biomacromolecules.2007,8:3115-3125
[41]Yuan WZ, Yuan J, Zheng S, Hong X. Synthesis, characterization, and controllable drug release of dendritic star-block copolymer by ring-opening polymerization and atom transfer radical polymerization. Polymer.2007,48:2585-2594
[42]Korhonen H, Helminen A, Seppala JV. Synthesis of polylactides in the presence of co-initiators with different numbers of hydroxyl groups. Polymer.2001,42:7541-7549
[43]Frauenrath H. Dendronized polymers-building a new bridge from molecules to nanoscopic objects. Prog Polym Sci.2005,30:325-384
[44]Frechet JMJ. Functional polymers and dendrimers:reactivity, molecular architecture, and interfacial energy. Science.1994,263:1710-1715
[45]Cordova A, Janda KD. Synthesis and Catalytic Antibody Functionalization of Dendrimers. J Am Chem Soc.2001,123:8248-8259
[46]Aoi K, Hatanaka T, Tsutsumiuchi K, Okada M, Imae T. Synthesis of a novel star-shaped dendrimer by radial-growth polymerization of sarcosine N-carboxyanhydride initiated with poly(trimethyleneimine) dendrimers. Macromol Rapid Commun.1999,20:378-382
[47]Jamshidi K, Hyon SH, Ikada Y. Thermal characterization of polylactides. Polymer.1988, 29:2229-2234
[1]王震,孔祥明,高峰等.基板受限条件F聚合物薄膜厚度对结晶的影响研究.高等学校化学学报,2003,24(3)：551-554.
[2]Qiao C. D., Zhao J. C., Jiang S. C. et al. Crystalline morphology evolut ion in PCL thin films. J. Polym. Sc. I, Polym. Phys.2005,43:1303-1309.
[3]LellingerD., FloudasG., Alig I., Shear induced crystallization in poly(caprolactone):effect of shear rate. Polymer,2003,44:5759-5769.
[4]Guo Q., Harrats C., Groeninckx G. et al. Miscibility, crystallization and real-time Small-angle X-ray scattering investigation of the semicrystalline morphology in thermosetting polymer blends. Polymer,2001,42:6031-6041.
[5]Chen H. L., Li L. J., OuYang W. C. et al. Spherulitic Crystallization Behavior of Poly(caprolactone) with a Wide Range of Molecula Weight. Macromolecules,1997, 30:1718-1722.
[6]Shichun Jiang, Xiangling Ji, Lijia An, et al. Crystallization behavior of PCL hybrid confined environment. Polymer.2000,42:3901-3907.
[7]Phillips P. J., Rensch G. J., Taylor K. D. Crystallization studies of poly(caprolactone).I. Morphology and kinetics. J. Polym. Sc. I, Polym. Phys.1987,25:1725-1740.
[8]蒙延峰,温慧颖,李宏飞等.聚己内酯的等温与非等温结晶动力学研究.高等学校化学学报,2006,27：2198-2203.
[9]高家武,段跃新,王身国,邱波.聚己内酯,聚乙二醇及其嵌段物的结晶行为.应用化学,1995,12：98-100.
[10]Gan Z. H., Zhang J., Jiang B. Z. Poly(caprolactone)/poly(ethylene oxide) diblock copolymer I. Isothermal crystallization and melting behavior. J. Appl. Polym. Sci.,1996, 59:961-967.
[11]Bogdanov B, Vidts A., Schacht E. Isothermal Crystallization of Poly(caprolactone-ethylene glycol) Block Copolymers. Macromolecules,1999,32: 726-731
[12]Chaoliang He, Jingru Sun, Jia Ma, et al. Composition Dependence of the Crystallization Behavior and Morphology of the Poly(ethylene oxide)-poly(caprolactone) Diblock Copolymer. Biomacromolecules,2006,7:3482-3489.
[13]Gan Z. H., Zhang J., Jiang B. Z. Poly(caprolactone)/poly(ethylene oxide) diblock copolymer Ⅱ. Nonisothermal crystallization and melting behavior. J. Appl. Polym. Sci., 1997,63:1793-1804
[14]Chaoliang He, Jingru Sun, Chao Deng et al. Study of the Synthesis, Crystallization, and Morphology of Poly(ethylene glyc01)-Poly(caprolactone) Diblock Copolymers. Biomacromolecules,2004,5:2042-2047.
[15]Bogdanov B, Vidts A., Van D. B. Synthesis and thermal properties of poly(ethylene glycol)-poly(caprolactone)copolymers. Polymer,1998,39:1631-1636.
[16]Letehford K, Burt H. A review of the formation and classification of amphiphilie block eopolymer nanopartieulate structures:micelles, nanospheres, rmnocapsules and polymersomes. Eur J Pharm Biopharm,2007,65(3): 259-269.
[17]Sinsh R, Jr Lillard JW. Nanopartiele-based targeted drug delivery. Exp Mol Pathol,2009, 86(3):215-223.
[18]Levine DH, Ghomghehian PP, FreudenbergJ. el al. Polymersomes:a new multi-functional tool for cancer diagnosis and therapy. Methads,2008,46(1):25-32.
[1]Joachim Herrmann, Roland Bodmeier, Biodegradable, somatostatin acetate containing microspheres prepared by various aqueous and non-aqueous solvent evaporation methods. European Journal of Pharmaceutics and Biopharmaceutics.1998 (45):75-82.
[2]Viswanathan N.B., Tomas P.A., Pandit J.K., et al., Preparation of non-porous microspheres with high entrapment efficiency of proteins by a (water-in-oil)-in-oil emulsion technique. J. Control. Release 1999,58 (1):9-20.
[3]Yang J.F., Qiu L.Y., Jin Y., et al., Thymosin-loaded enteric microspheresfor oral administration:Preparation and in vitro release studies. Int. J. Pharm.2005,301
[4]Carrasquillo K.G, Stanley A.M., Aponte-Carro J.C., et al., Non-aqueous encapsulation of excipient-stabilized spray-freeze dried BSA into poly(lactide-co-glycolide) microspheres results in release of native protein. J. Control. Release 2001,76 (3):199-208.
[5]方起程,方唯硕,紫杉醇的研究进展,中草药,1997,28(增刊)：1-5
[6]邱晓航,抗癌药物紫杉醇水溶性制剂的研究进展,中国生化药物杂志,2000,21(1)：44-45
[7]陈大兵,吕万良,杨天智等,紫杉醇表面修饰脂质纳米粒的制各和性质,北京大学学报(医学版),2002,34(11)：57-60
[8]Paola Crosasso, Manrizio Ceruti, Paola Brusa, et. al. Preparation, characterization and properties of sterically stabilized paclitaxel. containing liposomes, Journal ofControlled Release,2000,63(1-2):19-30
[9]张景勃,张志荣,紫杉醇靶向制剂的研究进展,中国药房,2001,12(7)：436-437
[10]李金亮,冯霞,刘斌等,聚乙二醇负载水溶性紫杉醇衍生物的合成,2001,34(61)：808-811
[11]陈大兵,杨天智,吕万良等,紫杉醇长循环固态脂质纳米粒的制备和体外研究,药学学报,2002,37(1)：54-58
[12]张景勃,张志荣,紫杉醇脂质体的制各和质量评价,华西药学杂志,2001 16(11)：23-24
[13]阎家麒,王惠杰,童岩等,紫杉醇微乳的研究,中国药学杂志,2000,35(3)：173-176
[14]熊学敏,曹王玉,康明等,紫杉醇微球制备的初步研究,中国新药杂志,2001,10(7)：517-519
[15]杨宇润,陈永林,王得宁等.丁苯-丁腈基聚氨酯的形态与性能.高分子学报.2002,12(6)：795-800
[16]Pankaj Pathak, Gaddamanugu L. Prasad, Mohammed J. Meziani, Attalla A. Joudeh, and Ya-Ping Sun, Nanosized Paclitaxel Particles from Supercritical Carbon Dioxide Processing and Their Biological Evaluation. Langmuir 2007, (23):2674-2679
[17]Mu L., Feng S. S.:Fabrication, characterization and in vitro release of paclitaxel (Taxol(?)) loaded poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique with lipid/cholesterol emulsifiers. Journal of Controlled Release,76,239-254 (2001).
[18]Lee L. Y., Wang C. H., Smith K. A.:Supercritical antisolvent production of biodegradable micro- and nanoparticles for controlled delivery of paclitaxel. Journal of Controlled Release,125,96-106 (2008).
[19]Lee J. Y., Cho E. C., Cho K.:Incorporation and release behavior of hydrophobic drug in functionalized poly(d,l-lactide)-block-poly(ethylene oxide) micelles. Journal of Controlled Release,94,323-335 (2004).
[20]Hemin Nie, Yilong Fu, Chi Hwa Wang, Paclitaxel and suramin-loaded core/shell microspheres in the treatment of brain tumors. Biomaterials,2010, (31) 8732-8740
[1]刘兵,恶性胶质瘤化学治疗新策略.中国神经肿瘤杂志.2004,2(1)：72-76
[2]杜小莉.治疗顽固性多形性成胶质细胞瘤的新药替莫唑胺.中国药学杂志.2000,2(35)：135
[3]Guerin C,Olivi A,Weingart JD,et al. Recent advances in brain tumor therapy:local intracerebral drug delivery by polymers[J]. Investigational New Drugs,2004,22(1):27～37.
[4]曹小毅,朱宏,微球中替莫唑胺含量测定方法的研究.化工之友.2007,3(11)：38-39
[2]Tomalia D.A, Baker H, Dewald J, Hall M, Kallos G, Martin S, Roeck J, Ryder J and Smith P, "A New Class of Polymers:Starburst-Dendritic Macromolecules", Polym. J., 17(1),117-132,1985.
[3]Newkome G.R, Yao Z.Q, Baker G.R and Gupta V.K, "Cascade molecules:A new approach to micelles, A", J. Org. Chem.,50(11),2003-2006,1985.
[4]Pushkar S, Philip A, Pathak K and Pathak D, "Dendrimers:Nanotechnology Derived Novel Polymers in Drug Delivery", Indian J. Pharm. Educ. Res.,40 (3),153-158,2006.
[5]Sakthivel T and Florence A.T, "Adsorption of Amphipathic Dendrons on Polystyrene Nanoparticles", Int. J. Pharm.,254,23-26,2003.
[6]Yiyun C, Zhenhua X, Minglu M and Tonguen X, "Dendrimers as Drug Carriers: Applications in Different Routes of Drug", J.Pharma.Sci.,97(1),123-143,2008.
[7]Hawker C and Frechet J.M.J, "A new convergent approach to monodisperse dendritic molecule" J. Chem. Soc. Chem. Commun,15,1010-1012,1990.
[8]Hawker C, Wooley K.L and Frechet J.M.J, J.Chem. Soc. Perkin. Trans.,1,1287-1289, 1993.
[9]Frechet J.M.J and Tomalia D.A, "Introduction to the Dendritic state", Dendrimers and other Dendritic Polymers, John Wiley & Sons Ltd,24-23,2001.
[10]Sonke S and Tomalia D.A, "Dendrimers in biomedical applications reflections on the Field", Advanced Drug Delivery Reviews,57,2106-2129,2005.
[11]Christine D, Ijeoma F.U and Andreas GS, "Dendrimers in gene delivery", Advanced Drug Delivery Reviews,57,2177-2202,2005.
[12]Freeman A.W and Frechet J.M.J, "Developments in the Accelerated Convergent Synthesis of Dendrimers", Dendrimers and other Dendritic Polymers Edited by Jean M. J. Fre'chet and Donald A. Tomalia,91-101.
[13]Barbara K. and Maria B., "Review Dendrimers:properties and applications", Acta Biochimica Polonica,48 (1),199-208,2001.
[14]R.P.Patel et al. "Dendrimers:A new innovation in drug delivery", Pharma Bio World, 42-52,2007.
[15]Boris D, Rubinstein M, "A self-consistent mean field model of a starburst dendrimer: dense core vs. dense shell", Macromolecules,29,7251-7260,1996.
[16]Chai M, Niu Y., Youngs W.J and Rinaldi P.L, "Structure and conformation of DAB dendrimers in solution via multidimensional NMR techniques", J. Am. Chem. Soc., 123,4670-4678,2001.
[17]Gupta U, Agashe H and Jain N.K, "Polypropylene imine dendrimer mediated solubility enhancement:effect of pH and functional groups of hydrophobes", J. Pharm. Sci.,10(3), 358-67,2007.
[18]Wang D.J and Imae T, "fluorescence emission from Dendrimer & its pH dependence", J. Am. Chem. Soc.,126(41),13204-13205,2004.
[19]Zinselmeyer B.H, Mackay S.P, Schatzlein A.G and Uchegbu I.F, "The lower-generation polypropylenimine dendrimers are effective gene-transfer agents", Pharm. Res.,19,960-967, 2002.
[20]Jevprasesphant R, Penny J, Jalal R, Attwood D, McKeown N.B and D'Emanuele A. "The influence of surface modification on the cytotoxicity of PAMAM dendrimers", Int. J. Pharm.,252,263-266,2003.
[21]Jevprasesphant R, Penny J, Jalal R, Attwood D, McKeown N.B and D'Emanuele A., "Engineering of dendrimer surfaces to enhance transepithelial transport and reduce cytotoxicity", Pharm. Res.20,1543-1550,2003.
[22]Satija J, Gupta U and Jain N.K "Pharmaceutical and biomedical potential of surface engineered dendrimers" Crit Rev Ther Drug Carrier Syst.,24 (3),257-306,2007.
[23]Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, Weener J.W, Meijer E.W, Paulus W and Duncan R, "Dendrimers:relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of I-125-labelled polyamidoamine dendrimers in vivo", J.Control. Release,65,133-148,2000.
[24]Uchegbu I.F, Sadiq L, Pardakhty A, El-Hammadi M, Gray A.I, Tetley L, Wang W, Zinselmeyer B.H and Schatzlein A.G, "Gene transfer with three amphiphilic glycol chitosans —the degree of polymerisation is the main controller of transfection efficiency", J. Drug Target.,12,527-539,2004.
[25]Brownlie A, Uchegbu I.F and Schatzlein A.G, "PEI-based vesicle-polymer hybrid gene delivery system with improved biocompatibility", Int. J. Pharm.,274,41-52,2004.
[26]Schatzlein A.G, Zinselmeyer B.H, Elouzi A, Dufes C, Chim Y.T, Roberts C.J, Davies M.C, Munro A, Gray A.I and Uchegbu I.F, "Preferential liver gene expression with polypropylenimine dendrimers", J. Control. Release,101,247-258,2005.
[27]Chen H.T, Neerman M.F, Parrish A.R and Simanek E.E, "Cytotoxicity, hemolysis, and acute in vivo toxicity of dendrimers based on melamine, candidate vehicles for drug delivery", J. Am. Chem. Soc.,126,10044-10048,2004.
[28]Gillies E.R. and Frechet J.M.J, "Dendrimers and dendritic polymers in drug delivery" Drug Discovery Today,10,35-43,2005.
[29]Esfand, R. and Tomalia, D.A. "Polyamidoamine (PAMAM) dendrimers:from biomimicry to drug delivery and biomedical applications". Drug Discov. Today,6,427-436, 2001.
[30]Jevpraesesphant, R. et al., "The influence of surface modification on the cytotoxicity of PAMAM dendrimers", Int.J. Pharm.,252,263-266,2003.
[31]Hawker, C.J. and Frechet, J.M.J. "Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules". J. Am.Chem. Soc.,112,7638-7647,1990.
[32]Liu, M. et al. "Water-soluble unimolecular micelles:their potential as drug delivery agents". J. Control. Release,65,121-131,2000.
[33]Liu, M. et al. "Water-soluble dendrimer-polyethylene glycol starlike conjugates as potential drug carriers". J. Polym. Sc i., A 37,3492-3503,1999.
[34]Haag, R. et al. "An approach to glycerol dendrimers and pseudo-dendritic polyglycerols" J. Am. Chem. Soc.,122,2954-2955,2000.
[35]Neerman M.F et al. "In vitro and in vivo evaluation of a melamine dendrimer as a vehicle for drug delivery". Int. J. Pharm.,281,129-132,2004.
[36]Caminade A.M, Laurent R. and Majoral J.P, "Characterization of dendrimers", Advanced Drug Delivery Reviews,57,2130-2146,2005.
[37]Mohammad N and Antony D, "Crossing cellular barriers using dendrimer nanotechnologies", Current Opinion in Pharmacology,6,522-527,2006.
[38]Lee S.C "Dendrimers In Nanobiological Devices", Dendrimers and other Dendritic Polymers Edited by Fre'chet J.M.J and Tomalia D.A.,547-554.
[39]Kleij A.W, Ford A, JastrzebskI H and Vankoten G, "Dendritic Polymer Applications: Catalysts", Edited by Fre'chet J.M.J and Tomalia D.A.,485-507.
[40]Kofoed J and Reymond J, "Dendrimers as artificial enzymes", Current Opinion in Chemical Biology,9,656-664,2005.
[51]N.K.Jain, Controlled and Novel drug delivery,04 Edition,236-237,21.
[52]S.P.Vyas and R.K.Khar, Targeted and Controlleddrug delivery,07 Edition,418.
[53]Kreuter J., Nefzger M., Liehl E., CzokR. andVoges R. (1983) J.Pharm sci.72,1146.
[54]Margel S. and Wiesel E. (1984) J.polym.sci.22,145.
[55]Wakiyama N., Juni K. and Nakano M.(1981)chem..pharm.Bull.29,3363.
[56]Sugibayashi K., Akimoto M., Moromoto Y.,Nadai T. and Kato Y.(1979) pharmacobiodyn.23,50.
[57]Yoshioka T., Hashida M., Muranishi S. andSezakiH. (1981) Int.J.pharm.8,131.
[58]Russel G.F. (1983) pharma.Int.4,260.
[59]Woodland J.H.R., Yolles S., Blake D.A., HetrichM.and Meyer F.J.(1973) J. Med.chem.16,897.
[60]Rojas J., Pinto. Alphandary H., LeoE., Pecqests.,couvreur P., Gulik A. and Fattal. E. (1999)Pharm Res.16,255.
[61]Albertson AC., Carlfors J. and Sturess on C.(1993) J. Appl.polym.Sci.62,695.
[62]Renbaum A. (1983) US patent 4,413,070.
[63]S.P.Vyas & R.K.Khar, Targeted & Controlleddrug delivery.2007 Edition,435.
[64]KoffUS patent (March21963) 3,080,292.
[65]John P.M and Becker. C.H. (1968) J.pharm.sci.57,584.
[66]Schugens C., Larvelle. N., Nihantn., GrandfilsC., Jerome R. and Teyssie. P. (1994) J.Control.Rel.32,161.
[67]Mathews B.R. and Nixon J.R.(1974)J.pharmPharmacrol.26,283.
[68]N.K.Jain, Advances in controlled & Novel drugdelivery,03 Edition,71.
[69]Venkatesh H. (1989) "A buccal delivery systemof Salbutamol Sulphate" M.Pharm; Budrinarayan, N. (1991) "Utilisation andEvaluation of plant products in pharmaceutical formulations".M.Pharm.
70] Tanaka, W; Akito, E; Yoshida, K.; Terada, T.andNinomiya, H. (1977) "pharmaceutical preparations for oral cavity administration" USpatent No.4059686.
[71]Ishida, M; Nambu, N.and Nagai, T. (1983a)"Highly viscous gel ointment containing carbapol for application to the oral mucosa".Chem..pharm Bull.,31:4561.
[72]Collins, A.E and Deasy, P.B (1990)"Bioadhesive lozenge for the improved delivery of cetypyridinium chloride".J.pharm.sci.,79(2):116-120.
[73]Save T. and Venkatachalam P. (1994)"Bioadhesive tablets of Nifedipine: Standardization of a novel buccoadhesiveerodible carrier". Drug Dev.Ind. pharm.,20(19): 3005-3014.
[74]Dev rajan,P.V;Gupta S.; Gandhi A.S.;Niphadkar,P.V. and Shah.(1999)"Trans mucosal drug delivery systems ofSalbutamol Sulfate." 26th Int.Symp. Control.Rel.Bioact.Mater.,650.
[75]Lopez, C.R; Portero, A.; Vila-Jato, J.C. andAlonso, M.J. (1998) "Design and Evaluation ofChitosan/Ethylcellulose mucoadhesive bilayered devices for buccal drug delivery."J.control.Rel.,55:143-152.
[76]Parodi, B.; Russo, E.; Caviglioli, G.; Cafaggi, S.and Binardi, G. (1996) "Development &characterization of a buccoadhesive dosage from of Oxydodone hydrochloride". Drug Dev.Ind.pharm.,22(5):445-450.
[77]Chien, Y.W.; Corbo, D.C. and Liv, J.C. (1991) "Mucosal delivery of progestational Steroids from a Controlled release device:in vitro/in vivo relationship."DrugDev.Ind.pharm.,17(17):2269-2290.
[78]Cassidy, J.P.; Landcert, N.M.and Quardos, E. (1993) "controlled buccal delivery of buprenorphine". J.control.Rel.,25:21-29.
[79]Dortune, B.; Ozer, L.and Vyanik, N.(1998) "Development and invitro Evaluation of buccoadhesive pindodlo tablet formulation." Drug Dev.Ind.pharm.,24(3):281-288.
[80]Guo, J.H. (1994) "Bioadhesive polymer buccal patches for buprenorphine controlled delivery:formulation in vitro adhesive and release properties". Drug Dev.Ind.pharm., 20(3):315-325.
[81]Nagai, T.; Machida, Y.; Suzuki Y.and Ikura, H. (1980) "Method & preparation for administration to the mucosa & preparation for administration to the mucosa of the oral or nasal cavity" US patent NO.4226848.
[82]Chein, YW.and Novir, M. (1996) "Mucosal adhesive device for long acting delivery of pharmaceutical combinations in oral cavity". US patent NO.5578315.
[83]Fabregas, J.L.and Garcia, N. (1995) "Invitro studies on buccoadhesive tablet formulations of hydro cortisone hemisuccinate". Drug Dev.Ind.pharm.,21(14):1689-1696.
[84]Rathbone, M.J.; Purve, R.:Ghazati, F.A.and HO, P.C. (1996) "In vivo techniques for studying the oral mucosa absorption characteristics of drugs in animals and humans." In Rathbone, M.J. (ed.), oral mucosal delivery systems, Marcel Dekker Inc.Newyork.,121-156.
[85]Lu, M.F.and Hui, H.W. (1996) "Delivery of rennin inhibitors through mouth mucosa" Drug Dev.Ind.pharm.,22 (11); 1167-1171.
[86]Yukimatsu, K.; Nozaki, Y.; Kakumoto, M.and Ohta, M. (1994) "Development of a transmucosal controlled release device for systemic delivery of antianginal drug sphar maco kinetics and pharmacodynamics". Drug Dev.Ind.pharm,20(4):503-534.
[87]Hussain, M.A; Aungst, B.J.; Kearney A. and Shefter, E. (1987) "Buccal and oral bioavailability of naloxone and naltrexone in rats". INT, J.pharm.,36:127.
[88]Oh, C.K. and Ritschel., W.A. (1999a) "Biopharmaceutical aspects of buccal absorption of insulin rabbits I. Effects of dose, size, Ph & sorption enhancers:in vivo in vitro correlation". Pharm.Res.,5-5-100.
[89]Oh, C.K. and Ritschel, W.A. (1988b) "Biopharmaceutical aspects of buccal absorption of insulin in rabbits II. Absorption characteristics of insulin through the buccal mucosa". pharma.Res.,5-5-100.
[90]Kellaway, I.W. and warren, S.I. (1991) "Mucoadhesive hydrogels". Proc.Intern.symp.Control.Rel.Bioact.Mater.,18:73.
[91]Ishida, M.:Nambu, N.and Nagai, T.(1983a) "Highly viscous gel ointment containing carbopol for application to the oral mucosa".Chem.pharm.Bull.,31:4561.
[92]Ishida, M.; Nambu, N. and Nagai, T. (1983b) "Ointment type oral mucosal dosage form of carbopol containing prednisolone for the treatment of aphtha". Chem.pharm.Bull.,31:1010.
[93]Hoogstrate, A.J., verhoef, J.C.; Tuk., B.;Pijpers, A.; Vercheijden,J.H.M.; Jungiger, H.E. andBodde, H.C. (1996b) "Invivo buccal delivery of fluorescein iso thiocyanate-dextran 4 457-460.
[94]Burnside, B.A; Keith, A.P. and snipes, W.(1989) "micro porous hollow fibers as a peptide delivery system via the bucca activity ".proceed.inter.symp.control. Rel.Bioact. mater.,16:94.
[95]Rathone, M.J. (1991a) "Human buccal absorption I.A method for Estimating the transfer kinetics of drugs W cross the human buccal membrane". Int.J.pharm.,69:103.
[96]N.Venkateswarlu, Biopharmaceutics and kinetics,2004 Edition,53,54.
[97]Widder K.J., Sanyci A.E., Ovadia H., and Paterson P.Q. (1979) Clin. Immuno. Immuno pathol.14.395.
[98]Funden berg H.H., Stites D.P., Caldwel J.L.and Wells J.V. (1978) In:Basic and clinical immunology,2 ed., Lange Medical, Los Altosca.
[99]Capron A.C., Locht C. and Fracchia G.N (1994) Vaccine.12,667; Edelman R. (1993) vaccine 11,1361; Drews J. (1984) Immunostimulantien, Klin. Wochenscher.62,254; Spier K.E. (1993) vaccine 11,1450.
[100]Nachts S. and Martin K. (1990) In:The microsponges a novel topical programmable delivery formulation, Marcel Dekker Inc., Newyork.,299.
[1]Gillies E. R., Edward D, Frchet J. M. J., Szoka F. C. Biological E valuation of Polyester Dendrimer:Poly(ethylene oxide) "Bow-Tie" Hybrids with Tunable Molecular Weight and Architecture. Mol Pharm.2005,2 (2):129-138
[2]Daniel W, Salah-Eddine S, Andholger F. Hyperbranched Polyglycerols:From the Controlled Synthesis of Biocompatible Polyether Polyols to Multipurpose Applications. Accounts of Chemical Rearch.2010,43 (1):129-141
[3]Zhang X.L, Hyperbranched aromatic polyesters:From synthesis to applications. Progress in Organic Coatings 2010,69:295-309
[4]Lu Tian, Paula T. Hammond. Comb-Dendritic Block Copolymers as Tree-Shaped Macromolecular Amphiphiles for Nanoparticle Self-Assembly. Chem Mater.2006,18 (17):3976-3984
[5]Henrik Ihre, Omayra L. Padilla De Jesus, Jean MJ Frechet. Fast and Convenient Divergent Synthesis of Aliphatic Ester Dendrimers by Anhydride Coupling. J Am Chem Soc.2001, 123:5908-5917
[1]Yang Y, Bajaj N, Xu PS, Ohn K, Tsifansky MD, Yeo Y. Development of highly porous large PLGA microparticles for pulmonary drug delivery. Biomaterials.2009,30(10): 1947-1953
[2]Nasongkla N, Shuai X, Ai H, Brent DW, John P, David AB, Gao J. cRGD-Functionalized Polymer Micelles for Targeted Doxorubicin Delivery. Angew Chem Int Ed.2004.43: 6323-6327
[3]Ouchi T, Toyohara M, Arimura H, Ohya Y Preparation of Poly(L-lactide)-Based Microspheres Having a Cationic or Anionic Surface Using Biodegradable Surfactants. Biomacromolecules.2002,3:885-888
[4]Deng C, Tian HY, Zhang PB, Sun J, Chen XS, Jing XB. Synthesis and Characterization of RGD Peptide Grafted Poly(ethylene glycol)-b-Poly(L-lactide)-b-Poly(L-glutamic acid) Triblock Copolymer. Biomacromolecules.2006,7:590-596
[5]Li SM, Garreau H, Pauvert B, McGrath J, Toniolo A, Vert M. Enzymatic Degradation of Block Copolymers Prepared from ε-Caprolactone and Poly(ethylene glycol). Biomacromolecules.2002,3:525-530
[6]Kwon GS, Kataoka K. Block copolymer micelles as long-circulating drug vehicles. Adv Drug Delivery Rev.1995,16:295-309.
[7]Li SM, Liu LJ, Garreau H, Vert M. Lipase-Catalyzed Biodegradation of Poly(ε-caprolactone) Blended with Various Polylactide-Based Polymers. Biomacromolecules.2003,4:372-377.
[8]Tabata Y. The importance of drug delivery systems in tissue engineering. Pharm Sci Technol Today.2000,3:80-89
[9]Sheridan MH, Shea LD, Peters MC, Mooney DJ. Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery. J Control Release.2000, 64:91-102
[10]Baldwin SP, Saltzman WM. Materials for protein delivery in tissue engineering. Adv Drug Delivery Rev.1998,33:71-86
[11]Whang KM, Goldstick TK, Healy KE. A biodegradable polymer scaffold for delivery of osteotropic factors. Biomaterials.2000,21:2545-2551
[12]Breitenbath A, Kissel T. Biodegradable comb polyesters Part 1 synthesis, characterization and structural analysis of poly(lactide) and poly(lactide-coglycolide) grafted onto water-soluble poly(vinyl alcohol) as backbone. Polymer.1998,39:3261-3271
[13]Luo YF, Wang YL, Niu XF, Shang JF. Evaluation of the cytocompatibility of butanediamine- and RGDS-grafted poly(dl-lactic acid). Eur Polym J.2008,44: 1390-1402
[14]Zhao YL, Cai Q, Jiang J, Shuai XT, Bei JZ, Chen CF, Xi F. Synthesis and thermal properties of novel star-shaped poly(L-lactide)s with starburst PAMAM-OH dendrimer macroinitiator. Polymer.2002,43:5819-5825
[15]Li YX, Volland C, Kissel T. Biodegradable brush-like graft polymers from poly(D，L-lactide) or poly(D,L-lactide-coglycolide) and charge-modified, hydrophilic dextrans as backbone—in-vitro degradation and controlled releases of hydrophilic macromolecules. Polymer.1998,39:3087-3097
[16]Breitenbach A, Pistel KF, Kissel T. Biodegradable comb polyesters. Part Ⅱ. Erosion and release properties of poly(vinyl alcohol)-g-poly(lactic-co-glycolic acid). Polymer.2000, 41:4781-4792
[17]Cai Q, Zhao YL, Bei JZ, Xi F, Wang SG. Synthesis and Properties of Star-Shaped Polylactide Attached to Poly(Amidoamine) Dendrimer. Biomacromolecules.2003,4, 828-834
[18]Chen HT, Neerman MF, Parrish AR, Simanek EE. Cytotoxicity, Hemolysis, and Acute in Vivo Toxicity of Dendrimers Based on Melamine, Candidate Vehicles for Drug Delivery. J Am Chem Soc.2004,126:10044-10048
[19]Okuda T, Kawakami S, Akimoto N, Niidome T, Yamashita F, Hashida M. J Control Release.2006,116:330-336
[20]Okuda T, Kawakami S, Maeie T, Niidome T, Yamashita F, Hashida M. PEGylated lysine dendrimers for tumor-selective targeting after intravenous injection in tumor-bearing mice. J Control Release.2006,114:69-77
[21]Gillies ER, Dy E, Frechet JMJ, Szoka FC. Biological Evaluation of Polyester Dendrimer:Poly(ethylene oxide) "Bow-Tie" Hybrids with Tunable Molecular Weight and Architecture. Mol Pharmaceut.2005,2:129-138
[22]Gillies ER, Frechet JMJ. Designing Macromolecules for Therapeutic Applications:Polyester Dendrimer-Poly(ethylene oxide) "Bow-Tie" Hybrids with Tunable Molecular Weight and Architecture. J Am Chem Soc.2002,124:14137-14146
[23]Guillaudeu SJ, Fox ME, Haidar YM, Dy EE, Szoka FC, Frechet JMJ. PEGylated Dendrimers with Core Functionality for Biological Applications. Bioconjuag Chem. 2008,19:461-469
[24]Cai Q, Wan YQ, Bei JZ, Wang SG. Synthesis and characterization of biodegradable polylactide-grafted dextran and its application as compatilizer. Biomaterials.2003,24: 3555-3562
[25]Finne A, Albertsson AC. Controlled Synthesis of Star-Shaped L-Lactide Polymers Using New Spirocyclic Tin Initiators. Biomacromolecules.2002,3:684-490
[26]Kricheldorf HR, Hachmann TH, Schwarz G. Telechelic and Star-Shaped Poly (L-lactide)s by Means of Bismuth(III) Acetate as Initiator. Biomacromolecules.2004,5: 492-496
[27]Ydens I, Degee P, Dubois P, Libiszowski J, Duda A, Penczek S. Combining ATRP of Methacrylates and ROP of L,L-Dilactide and ε-Caprolactone Macromolecular Chemistry and Physics. Macromol Chem Phys.2003,204:171-179
[28]Teramoto Y, Nishio Y. Cellulose diacetate-graft-poly(lactic acid)s:synthesis of wide-ranging compositions and their thermal and mechanical properties. Polymer.2003, 44:2701-2709
[29]Nouvel C, Dubois P, Dellacherie E, Six JL. Controlled synthesis of amphiphilic biodegradable polylactide-grafted dextran copolymers. J Polym Sci Part A:Polym Chem. 2004,42:2577-2588
[30]Du YJ, Lemstra PJ, Nijenhuis AJ, Van Aert HAM, Bastiaansen C. ABA Type Copolymers of Lactide with Poly (ethylene glycol). Kinetic, Mechanistic, and Model Studies. Macromolecules.1995,28:2124-2132
[31]Yang JL, Zhao T, Zhou YC, Liu LJ, Li G, Zhou EL, Chen XS. Single Crystals of the Poly(1-lactide) Block and the Poly(ethylene glycol) Block in Poly(1-lactide)-poly(ethylene glycol) Diblock Copolymer. Macromolecules.2007,40:2791-2797
[32]Yasugi KJ, Nakamura T, Nagasaki Y, Kato M, Kataoka K. Sugar-Installed Polymer Micelles:Synthesis and Micellization of Poly(ethylene glycol)-Poly(D,L-lactide) Block Copolymers Having Sugar Groups at the PEG Chain End. Macromolecules.1999,32: 8024-8032
[33]Han DK, Hubbell JA. Synthesis of Polymer Network Scaffolds from L-Lactide and Poly(ethylene glycol) and Their Interaction with Cells. Macromolecules.1997,30: 6077-6083
[34]Schindler A, Hibionada YM, Pitt CG. Aliphatic polyesters. Ⅲ. Molecular weight and molecular weight distribution in alcohol-initiated polymerizations of ε-caprolactone. J Polym Sci Part A:Polym Chem.1982,20:319-326
[35]Zhang XC, MacDonald DA, Mattheus FA, McAuley GKB. Mechanism of lactide polymerization in the presence of stannous octoate:The effect of hydroxy and carboxylic acid substances. J Polym Sci Part A:Polym Chem.1994,32:2965-2970
[36]Nijenhuis AJ, Grijpma DW, Pennings AJ. Lewis acid catalyzed polymerization of L-lactide. Kinetics and mechanism of the bulk polymerization. Macromolecules.1992, 25:6419-6424
[37]Ryner M, Stridsberg K, Albertsson AC, Von Schenck H, Svensson M. Mechanism of Ring-Opening Polymerization of 1,5-Dioxepan-2-one and L-lactide with Stannous 2-Ethylhexanoate. A Theoretical Study. Macromolecules.2001,34:3877-3881
[38]Kowalski A, Duda A, Penczek S. Mechanism of Cyclic Ester Polymerization Initiated with Tin (Ⅱ) Octoate.2. Macromolecules Fitted with Tin (Ⅱ) Alkoxide Species Observed Directly in MALDI-TOF Spectra. Macromolecules.2000,33:689-695
[39]Gottschalk G, Frey H. Hyperbranched Polylactide Copolymers. Macromolecules.2006, 39:1719-1723
[40]Numata K, Srivastava RK, Finne WA, Albertsson AC, Doi Y, Abe H. Branched Poly(lactide) Synthesized by Enzymatic Polymerization:Effects of Molecular Branches and Stereochemistry on Enzymatic Degradation and Alkaline Hydrolysis. Biomacromolecules.2007,8:3115-3125
[41]Yuan WZ, Yuan J, Zheng S, Hong X. Synthesis, characterization, and controllable drug release of dendritic star-block copolymer by ring-opening polymerization and atom transfer radical polymerization. Polymer.2007,48:2585-2594
[42]Korhonen H, Helminen A, Seppala JV. Synthesis of polylactides in the presence of co-initiators with different numbers of hydroxyl groups. Polymer.2001,42:7541-7549
[43]Frauenrath H. Dendronized polymers-building a new bridge from molecules to nanoscopic objects. Prog Polym Sci.2005,30:325-384
[44]Frechet JMJ. Functional polymers and dendrimers:reactivity, molecular architecture, and interfacial energy. Science.1994,263:1710-1715
[45]Cordova A, Janda KD. Synthesis and Catalytic Antibody Functionalization of Dendrimers. J Am Chem Soc.2001,123:8248-8259
[46]Aoi K, Hatanaka T, Tsutsumiuchi K, Okada M, Imae T. Synthesis of a novel star-shaped dendrimer by radial-growth polymerization of sarcosine N-carboxyanhydride initiated with poly(trimethyleneimine) dendrimers. Macromol Rapid Commun.1999,20:378-382
[47]Jamshidi K, Hyon SH, Ikada Y. Thermal characterization of polylactides. Polymer.1988, 29:2229-2234
[1]王震,孔祥明,高峰等.基板受限条件F聚合物薄膜厚度对结晶的影响研究.高等学校化学学报,2003,24(3)：551-554.
[2]Qiao C. D., Zhao J. C., Jiang S. C. et al. Crystalline morphology evolut ion in PCL thin films. J. Polym. Sc. I, Polym. Phys.2005,43:1303-1309.
[3]LellingerD., FloudasG., Alig I., Shear induced crystallization in poly(caprolactone):effect of shear rate. Polymer,2003,44:5759-5769.
[4]Guo Q., Harrats C., Groeninckx G. et al. Miscibility, crystallization and real-time Small-angle X-ray scattering investigation of the semicrystalline morphology in thermosetting polymer blends. Polymer,2001,42:6031-6041.
[5]Chen H. L., Li L. J., OuYang W. C. et al. Spherulitic Crystallization Behavior of Poly(caprolactone) with a Wide Range of Molecula Weight. Macromolecules,1997, 30:1718-1722.
[6]Shichun Jiang, Xiangling Ji, Lijia An, et al. Crystallization behavior of PCL hybrid confined environment. Polymer.2000,42:3901-3907.
[7]Phillips P. J., Rensch G. J., Taylor K. D. Crystallization studies of poly(caprolactone).I. Morphology and kinetics. J. Polym. Sc. I, Polym. Phys.1987,25:1725-1740.
[8]蒙延峰,温慧颖,李宏飞等.聚己内酯的等温与非等温结晶动力学研究.高等学校化学学报,2006,27：2198-2203.
[9]高家武,段跃新,王身国,邱波.聚己内酯,聚乙二醇及其嵌段物的结晶行为.应用化学,1995,12：98-100.
[10]Gan Z. H., Zhang J., Jiang B. Z. Poly(caprolactone)/poly(ethylene oxide) diblock copolymer I. Isothermal crystallization and melting behavior. J. Appl. Polym. Sci.,1996, 59:961-967.
[11]Bogdanov B, Vidts A., Schacht E. Isothermal Crystallization of Poly(caprolactone-ethylene glycol) Block Copolymers. Macromolecules,1999,32: 726-731
[12]Chaoliang He, Jingru Sun, Jia Ma, et al. Composition Dependence of the Crystallization Behavior and Morphology of the Poly(ethylene oxide)-poly(caprolactone) Diblock Copolymer. Biomacromolecules,2006,7:3482-3489.
[13]Gan Z. H., Zhang J., Jiang B. Z. Poly(caprolactone)/poly(ethylene oxide) diblock copolymer Ⅱ. Nonisothermal crystallization and melting behavior. J. Appl. Polym. Sci., 1997,63:1793-1804
[14]Chaoliang He, Jingru Sun, Chao Deng et al. Study of the Synthesis, Crystallization, and Morphology of Poly(ethylene glyc01)-Poly(caprolactone) Diblock Copolymers. Biomacromolecules,2004,5:2042-2047.
[15]Bogdanov B, Vidts A., Van D. B. Synthesis and thermal properties of poly(ethylene glycol)-poly(caprolactone)copolymers. Polymer,1998,39:1631-1636.
[16]Letehford K, Burt H. A review of the formation and classification of amphiphilie block eopolymer nanopartieulate structures:micelles, nanospheres, rmnocapsules and polymersomes. Eur J Pharm Biopharm,2007,65(3): 259-269.
[17]Sinsh R, Jr Lillard JW. Nanopartiele-based targeted drug delivery. Exp Mol Pathol,2009, 86(3):215-223.
[18]Levine DH, Ghomghehian PP, FreudenbergJ. el al. Polymersomes:a new multi-functional tool for cancer diagnosis and therapy. Methads,2008,46(1):25-32.
[1]Joachim Herrmann, Roland Bodmeier, Biodegradable, somatostatin acetate containing microspheres prepared by various aqueous and non-aqueous solvent evaporation methods. European Journal of Pharmaceutics and Biopharmaceutics.1998 (45):75-82.
[2]Viswanathan N.B., Tomas P.A., Pandit J.K., et al., Preparation of non-porous microspheres with high entrapment efficiency of proteins by a (water-in-oil)-in-oil emulsion technique. J. Control. Release 1999,58 (1):9-20.
[3]Yang J.F., Qiu L.Y., Jin Y., et al., Thymosin-loaded enteric microspheresfor oral administration:Preparation and in vitro release studies. Int. J. Pharm.2005,301
[4]Carrasquillo K.G, Stanley A.M., Aponte-Carro J.C., et al., Non-aqueous encapsulation of excipient-stabilized spray-freeze dried BSA into poly(lactide-co-glycolide) microspheres results in release of native protein. J. Control. Release 2001,76 (3):199-208.
[5]方起程,方唯硕,紫杉醇的研究进展,中草药,1997,28(增刊)：1-5
[6]邱晓航,抗癌药物紫杉醇水溶性制剂的研究进展,中国生化药物杂志,2000,21(1)：44-45
[7]陈大兵,吕万良,杨天智等,紫杉醇表面修饰脂质纳米粒的制各和性质,北京大学学报(医学版),2002,34(11)：57-60
[8]Paola Crosasso, Manrizio Ceruti, Paola Brusa, et. al. Preparation, characterization and properties of sterically stabilized paclitaxel. containing liposomes, Journal ofControlled Release,2000,63(1-2):19-30
[9]张景勃,张志荣,紫杉醇靶向制剂的研究进展,中国药房,2001,12(7)：436-437
[10]李金亮,冯霞,刘斌等,聚乙二醇负载水溶性紫杉醇衍生物的合成,2001,34(61)：808-811
[11]陈大兵,杨天智,吕万良等,紫杉醇长循环固态脂质纳米粒的制备和体外研究,药学学报,2002,37(1)：54-58
[12]张景勃,张志荣,紫杉醇脂质体的制各和质量评价,华西药学杂志,2001 16(11)：23-24
[13]阎家麒,王惠杰,童岩等,紫杉醇微乳的研究,中国药学杂志,2000,35(3)：173-176
[14]熊学敏,曹王玉,康明等,紫杉醇微球制备的初步研究,中国新药杂志,2001,10(7)：517-519
[15]杨宇润,陈永林,王得宁等.丁苯-丁腈基聚氨酯的形态与性能.高分子学报.2002,12(6)：795-800
[16]Pankaj Pathak, Gaddamanugu L. Prasad, Mohammed J. Meziani, Attalla A. Joudeh, and Ya-Ping Sun, Nanosized Paclitaxel Particles from Supercritical Carbon Dioxide Processing and Their Biological Evaluation. Langmuir 2007, (23):2674-2679
[17]Mu L., Feng S. S.:Fabrication, characterization and in vitro release of paclitaxel (Taxol(?)) loaded poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique with lipid/cholesterol emulsifiers. Journal of Controlled Release,76,239-254 (2001).
[18]Lee L. Y., Wang C. H., Smith K. A.:Supercritical antisolvent production of biodegradable micro- and nanoparticles for controlled delivery of paclitaxel. Journal of Controlled Release,125,96-106 (2008).
[19]Lee J. Y., Cho E. C., Cho K.:Incorporation and release behavior of hydrophobic drug in functionalized poly(d,l-lactide)-block-poly(ethylene oxide) micelles. Journal of Controlled Release,94,323-335 (2004).
[20]Hemin Nie, Yilong Fu, Chi Hwa Wang, Paclitaxel and suramin-loaded core/shell microspheres in the treatment of brain tumors. Biomaterials,2010, (31) 8732-8740
[1]刘兵,恶性胶质瘤化学治疗新策略.中国神经肿瘤杂志.2004,2(1)：72-76
[2]杜小莉.治疗顽固性多形性成胶质细胞瘤的新药替莫唑胺.中国药学杂志.2000,2(35)：135
[3]Guerin C,Olivi A,Weingart JD,et al. Recent advances in brain tumor therapy:local intracerebral drug delivery by polymers[J]. Investigational New Drugs,2004,22(1):27～37.
[4]曹小毅,朱宏,微球中替莫唑胺含量测定方法的研究.化工之友.2007,3(11)：38-39