PLGA/TiO_2纳米药物缓释载体的研究
摘要
本文将可生物降解材料乳酸和羟基乙酸的共聚物(PLGA)用不同的方法引入到TiO_2纳米粒子表面上,制备了PLGA/TiO2纳米有机-无机杂化材料,目的是以此为载体吸附包裹胰岛素或其他药物,随着PLGA的降解,缓慢释放药物,以达到药物长效缓释的作用,同时提高药物缓释微球的载药量和包封率。研究工作如下：
(1)用硅烷偶联剂氨丙基三乙氧基硅烷(KH550)对二氧化钛表面进行预处理,接着与带有高活性端基的聚乳酸-羟基乙酸共聚物(PLGA)反应,制备PLGA/TiO2有机-无机杂化纳米材料。通过研究表明,PLGA/TiO2有机-无机杂化纳米材料中PLGA通过酰胺键键合接枝到Ti02纳米粒子的表面；PLGA接枝量为13.2%左右；通过接枝低分子量的聚合物,纳米粒子的分散性得到较好的改善,无明显团聚现象。
(2)通过实验将磺酸基引入PLGA分子链上,制得璜化PLGA,接着采用溶胶-凝胶技术,将璜化PLGA与二氧化钛凝胶反应,制备璜化PLGA/TiO2(SPLGA/TiO2)有机-无机杂化材料。研究表明,通过纳米Ti02表面羟基与PLGA的磺酸基上的氢离子的键合作用,低分子量的PLGA接枝到TiO2纳米粒子的表面；PLGA接枝量为20%左右；杂化材料纳米粒子分布均匀,无明显团聚现象；PLGA接枝在Ti02表面形成包裹层,有效的改善了TiO2的分散性和均一性。由细胞实验可知,PLGA/TiO2有机-无机杂化材料的生物相容性良好,适宜作为药物控制体系中的药物载体。
(3)研究了PLGA/TiO2杂化材料载药缓释体系中的应用。首先用杂化材料纳米粒子吸附溶液中的BSA制备纳米级的药物颗粒,然后运用水包油包固体(S/0/W)乳化法将药物粒子用可生物降解的高分子材料PLGA包裹起来制成蛋白药物控制释放制剂,同时用纳米二氧化钛作为对比实验。通过紫外和SEM分析可知,纳米材料吸附蛋白药物后的产物仍为纳米粒子。与纯二氧化钛相比,在二氧化钛表面接枝PLGA后,杂化材料的BSA吸附量较高,由43.31%提高到81.34%。将两种材料吸附BSA后的药物粒子用水包油包固体乳化法制备成聚合物微球,均具有很高的包封率,大于90%；但杂化材料载药微球的载药量由9.71%提高到14.63%,包封率由90.51%提高到97.53%。且在体外释放行为中突释较小。
In order to get high bioactive and good drug delivery carrier, novel nano bio-degradable and the organic-inorganic hybrid materials with nano-titanium dioxide. The surface modification process and PLGA was carried further to increase their interface compatibility. In addition, the materials behavior was characterized and analysis. and the hybrid materials biocompatibility and drug delivery carriers were studied
(1) In the first step, the y-Aminopropyltriethoxysilane (KH550) was grafted on the surface of titanium dioxide, and then reacted with high activity-terminated poly(lactic-acid-glycolic-acid) (PLGA), prepared the PLGA/TiO2 organic-inorganic hybrid nano-materials. The research results shows that, the PLGA bonded through the amide bond grafted onto the surface of TiO2 nanoparticles in the PLGA/TiO2 organic-inorganic hybrid nano-materials, PLGA grafted amount of 13.2%, and the hybrid material dispersion had a better improve, and no obvious agglomeration.
(2) First of all, PLGA was modified into sulfuric acid terminated, and reacted with titanium dioxide sol-gel through the sol-gel technology, perpetrated the PLGA/TiO2(SPLGA/TiO2) organic-inorganic hybrid materials. The Studies results show that, SPLGA/TiO2 organic-inorganic hybrid materials, sulfuric acid terminated PLGA was successful prepared and grafted on the surface of TiO2 nanoparticles through amide. PLGA grafted amount of about 20%, SEM photographs shows that hybrid materials has a good dispersion, no obvious agglomeration. PLGA grafted on TiO2 surface was formatted parcel layer, effectively improved the dispersion of TiO2 and homogeneity, and SPLGA/TiO2 organic-inorganic hybrid materials had excellent biocompatibility which we can see from the cells experiments and suit as a drug carriers in the drug control systems.
(3) SPLGA/TiO2 microspheres were prepared by firstly absorbing model drug BSA onto SPLGA/TiO2 nano particles and then coating with PLGA via S/O/W method, compared with nano-TiO2. Using UV-Vis and TEM, the absorbing behaviors of BSA onto nano particles and the impact of preparation method on the drug loading efficiency and in vitro controlled drug release were studied. The results showed that the two kinds microspheres all had a high encapsulation efficiecy, greater than 90%. SPLGA/TiO2 nano particles had a higher BSA adsorption, increased from 43.31% to 81.34%. The SPLGA/TiO2 microspheres had a high drug loading and a smaller burst in vitro behavior.
(1)用硅烷偶联剂氨丙基三乙氧基硅烷(KH550)对二氧化钛表面进行预处理,接着与带有高活性端基的聚乳酸-羟基乙酸共聚物(PLGA)反应,制备PLGA/TiO2有机-无机杂化纳米材料。通过研究表明,PLGA/TiO2有机-无机杂化纳米材料中PLGA通过酰胺键键合接枝到Ti02纳米粒子的表面；PLGA接枝量为13.2%左右；通过接枝低分子量的聚合物,纳米粒子的分散性得到较好的改善,无明显团聚现象。
(2)通过实验将磺酸基引入PLGA分子链上,制得璜化PLGA,接着采用溶胶-凝胶技术,将璜化PLGA与二氧化钛凝胶反应,制备璜化PLGA/TiO2(SPLGA/TiO2)有机-无机杂化材料。研究表明,通过纳米Ti02表面羟基与PLGA的磺酸基上的氢离子的键合作用,低分子量的PLGA接枝到TiO2纳米粒子的表面；PLGA接枝量为20%左右；杂化材料纳米粒子分布均匀,无明显团聚现象；PLGA接枝在Ti02表面形成包裹层,有效的改善了TiO2的分散性和均一性。由细胞实验可知,PLGA/TiO2有机-无机杂化材料的生物相容性良好,适宜作为药物控制体系中的药物载体。
(3)研究了PLGA/TiO2杂化材料载药缓释体系中的应用。首先用杂化材料纳米粒子吸附溶液中的BSA制备纳米级的药物颗粒,然后运用水包油包固体(S/0/W)乳化法将药物粒子用可生物降解的高分子材料PLGA包裹起来制成蛋白药物控制释放制剂,同时用纳米二氧化钛作为对比实验。通过紫外和SEM分析可知,纳米材料吸附蛋白药物后的产物仍为纳米粒子。与纯二氧化钛相比,在二氧化钛表面接枝PLGA后,杂化材料的BSA吸附量较高,由43.31%提高到81.34%。将两种材料吸附BSA后的药物粒子用水包油包固体乳化法制备成聚合物微球,均具有很高的包封率,大于90%；但杂化材料载药微球的载药量由9.71%提高到14.63%,包封率由90.51%提高到97.53%。且在体外释放行为中突释较小。
In order to get high bioactive and good drug delivery carrier, novel nano bio-degradable and the organic-inorganic hybrid materials with nano-titanium dioxide. The surface modification process and PLGA was carried further to increase their interface compatibility. In addition, the materials behavior was characterized and analysis. and the hybrid materials biocompatibility and drug delivery carriers were studied
(1) In the first step, the y-Aminopropyltriethoxysilane (KH550) was grafted on the surface of titanium dioxide, and then reacted with high activity-terminated poly(lactic-acid-glycolic-acid) (PLGA), prepared the PLGA/TiO2 organic-inorganic hybrid nano-materials. The research results shows that, the PLGA bonded through the amide bond grafted onto the surface of TiO2 nanoparticles in the PLGA/TiO2 organic-inorganic hybrid nano-materials, PLGA grafted amount of 13.2%, and the hybrid material dispersion had a better improve, and no obvious agglomeration.
(2) First of all, PLGA was modified into sulfuric acid terminated, and reacted with titanium dioxide sol-gel through the sol-gel technology, perpetrated the PLGA/TiO2(SPLGA/TiO2) organic-inorganic hybrid materials. The Studies results show that, SPLGA/TiO2 organic-inorganic hybrid materials, sulfuric acid terminated PLGA was successful prepared and grafted on the surface of TiO2 nanoparticles through amide. PLGA grafted amount of about 20%, SEM photographs shows that hybrid materials has a good dispersion, no obvious agglomeration. PLGA grafted on TiO2 surface was formatted parcel layer, effectively improved the dispersion of TiO2 and homogeneity, and SPLGA/TiO2 organic-inorganic hybrid materials had excellent biocompatibility which we can see from the cells experiments and suit as a drug carriers in the drug control systems.
(3) SPLGA/TiO2 microspheres were prepared by firstly absorbing model drug BSA onto SPLGA/TiO2 nano particles and then coating with PLGA via S/O/W method, compared with nano-TiO2. Using UV-Vis and TEM, the absorbing behaviors of BSA onto nano particles and the impact of preparation method on the drug loading efficiency and in vitro controlled drug release were studied. The results showed that the two kinds microspheres all had a high encapsulation efficiecy, greater than 90%. SPLGA/TiO2 nano particles had a higher BSA adsorption, increased from 43.31% to 81.34%. The SPLGA/TiO2 microspheres had a high drug loading and a smaller burst in vitro behavior.
引文
[I]Langer R. Drug delivery and targeting. Nature,1998,392:5-10.
[2]Brouwers JRBJ. Advanced and controlled drug delivery systems in clinical disease management. Pharmacy World & Science,1996,18:153-162.
[3]Deboer A and Breimer D. The blood-brain-barrier-clinical implications for drug-delivery to the brain. J. Roy. Coll. Phys. Lond.,1994,28:502-506.
[4]Uhrich K. E., Cannizzaro S. M., Langer R. S. Polymeric Systems for Controlled Drug Release. Chem. Rev.,1999,99:3181-3198.
[5]Jayanth P. and Vinod L. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Advanced Drug Delivery Reviews,2003,55:329-347.
[6]Dang W., Colvin 0., Brem H., et al. Covalent coupling of methotrexate to dextran enhances the penetration of cytotoxicity into a tissue-like matrix. Cancer Res.,1994,54:1729-1735.
[6]Walter K., Tamargo R., Olivi A., et al. Intratumoral chemotherapy. Neurosurgery,1995,37:1129-1145.
[7]Katayama N., Tanaka R., Ohno Y., et al. Implantable slow-release cyclosporine A (CYA) delivery system to thoracic lymph duct. Int. J. Pharm., 1995,115:87-93.
[8]Wagenaar B. and Muller B. Piroxicam release from spray-dried biodegradable microspheres. Biomaterials,1994,15:49-54.
[9]Conforti A., Bertani S., Lussignoli S., et al. Anti-inflammatory activity of polyphosphazene-based naproxen slow-release systems. J. Pharm. Pharmacol. 1996,48:468-473.
[10]Schierholz J., Rump A., and Pulverer G. New antiinfectious biomaterials-ciprofloxacin containing polyurethanes as potential drug delivery systems to prevent foreign-body infections. Drug Res.,1997,47: 70-74.
[11]Maniar M., Domb A., Haffer A., and Shah J. Controlled-release of a local-anesthetic from fatty-acid dimer based polyanhydride. J. Control. Release,1994,30:233-239.
[12]Johnson 0., Cleland J., Lee H., Charnis M., et al. A month-long effect from a single injection of microencapsulated human growth hormone. Nat. Med., 1996,2:795-799.
[13]Mcgee J., Davis S., and Ohagan D. The immunogenicity of a model protein entrapped in poly(lactide-co-glycolide) microparticles prepared by a novel phase-separation technique. J. Control. Release,1994,31:55-60.
[14]Sinha V. and Trehan A. Biodegradable microspheres for protein delivery. J. Control. Release,2003,90:261-280.
[15]Chu L. Y., Li Y., Zhu J. H., et al. Control of pore size and permeability of a glucose-responsive gating membrane for insulin delivery. J. Control. Release,2004,97:43-53.
[16]Traitel T., Cohen Y., and Kost J. Characterization of glucose-sensitive insulinrelease systems in simulated in vivo conditions. Biomaterials,2000, 21:1679-1687.
[17]李赛. 高分子纳米粒子在靶向药物载体中的研究进展. 生物医学工程学杂志,2004,21(3)：495-497.
[18]Birnbaum D., Kosmala J. Controlled release of β-estradiol from PLGA microparticles:the effect of organic phase solvent on encapsulation and realease. Journal of Controlled Release,2000,65:375.
[19]张志清,杨秀岭,樊德厚.抗癌药物白蛋白微球的研究进展.中国药师,1999,2(4)：195-197.
[20]盛洁, 山登布卡, 谢蜀生等. 单克隆抗体BDI-1导向的阿霉素白蛋白毫微球对人膀胱癌细胞的特异杀伤活性. 药学学报,1995,30(9)：706.
[21]Rihova B. Recepto-mediated targeted drug or toxin delivery. Advanced Drug Delivery Reviews,1998,29 (3):273.
[22]Yukiko N., Hiroyuki Y., Lymphatic targeting with nanoparticulate system. Advanced Drug Delivery Reviews,2001,47(1):55.
[23]Janes K.A., Calvo P., Alonso M. J. Polyaccharide colloidal particles as delivery systems for macro-molecules. Advanced Drug Delivery Reviews,2001, 47(1):83.
[24]Serizawa T., Chen M. Q., Akashl M. Graft copolymers having hydrophobic backbone and hydrophilic branches poly(strene) nanospheres with novel thermsensitive poly (N-vinylisobu-tyramide)s on their surfaces. J Polym Sci Part A:Polym Chem,1998,36:2581.
[25]Duncan R. and Spreafico F. Polymer conjugates-pharmacokinetic considerations for design and development. Clin. Pharmacokinet.,1994,27: 290-306.
[26]Langer R. New methods of drug delivery. Science,1990,249:1527-1533.
[27]Khandare J. and Minko T. Polymer-drug conjugates:Progress in polymeric prodrugs. Prog. Polym. Sci.,2006,31:359-397.
[28]David A., Kopeckova P., Minko T., et al. Design of a multivalent galactoside ligand for selective targeting of hpma copolymer-doxorubicin conjugates to human colon cancer cells. Eur. J. Cancer,2004,40:148-157.
[29] Satchi-Fainaro R., Wrasidlo W., Lode H., and Shabat D. Synthesis and characterization of a catalytic antibody-HPMA copolymerconjugate as a tool for tumor selective prodrug activation. Bioorg. Med. Chem.,2002,10:3023-3029.
[30]Wichterle 0. and Lim D. Hydrophilic gels in biologic use. Nature,1960, 185:117-118.
[31]Park K., Shalaby W. S. W., and Park H. Biodegradable hydrogels for drug delivery. PA:Lancaster,1993.
[32]Hoffman A. S., Schmer G., Harris C., and Kraft W. G. Covalent binding of biomolecules to radiation-grafted hydrogels on inert polymer surfaces. Trans. Am. Soc. Artif. Intern. Organs,1972,18:10-18.
[33]Harland R. S. and Prudhomme R. K. Polyelectrolyte gels:Properties, preparation, and applications. Washington D C:American Chemical Society,1992.
[34]Kamath K. and Park K. Biodegradable hydrogels in drug delivery. Advanced Drug Delivery Reviews,1993,11(1-2):59-84.
[35]Campoccia D., Doherty P., Radice M., et al. Semisynthetic resorbable materials from hyaluronan esterification. Biomaterials,1998,19:2101-27.
[36]Prestwich G. D., Marecak D. M., Marecak J. F., Verpenetracruysse K. P., and Ziebell M. R. Controlled chemical modification of hyaluronic acid. Journal of Controlled Release,1998,53:93-103.
[37]Hennink W. E. and Nostrum C. F.V. Novel crosslinking methods to design hydrogels. Adv. Drug Del. Rev,2002,54:13-36.
[38]Park K. and Park H. Smart Hydrogels. In:J.C. Salamone (Ed.), Concise Polymeric Materials Encyclopedia, CRC Press, Boca Raton,1999, pp.1476-8.
[39]Qiu Y. and Park K. Environment-sensitive hydrogels for drug delivery. Adv. Drug Del. Rev.,2001,53:321-339.
[40]Gupta P., Vermani K., and Garg S.. Hydrogels:From controlled release to pH-responsive drug delivery. Drug Discov. Today,2002,7:569-579.
[41]Lowman A.M. and Peppas N. A. Hydrogels, in Encyclopaedia of controlled drug delivery, E Mathiowitz, Ed. John Wiley & Sons.1999,397-418.
[42]Kost J. Intelligent drug delivery systems, in Encyclopaedia of controlled drugdelivery, E Mathiowitz, Edi. John Wiley & Sons.1999,445-459.
[43]Ishihara K., Kobayashi M., Ishimaru N., and Shinohara I. Glucose induced permeation control of insulin through a complex membrane consisting of immobilized glucose oxidase and a poly(amine). Polym. J.,1984,16:625-631.
[44]Ishihara K. and Matsui K. Glucose-responsive insulin release from polymer capsule. J. Polym. Sci. Polym. Lett. Ed.,1986,24:413-417.
[45]Allemann E., Gurny R., Doelker E., et al. Distribution, kinetics and elimination of radioactivity after intravenous and intramuscular injection of 14C-savoxepine loaded poly(L-lactic acid) nanospheres to rats. Journal of Controlled Release 1994,29(1-2):97-104.
[46]Mu L. and Feng S. S. A novel controlled release formulation for the anticancer drug paclitaxel (Taxol(?)):PLGA nanoparticles containing vitamin E TPGS. Journal of Controlled Release,2003,86:33-48.
[47]Barrio G. G., Novo F. J., and Irache J. M. Loading of plasmid DNA into PLGA microparticles using TROMS (Total Recirculation One-Machine System): evaluation of its integrity and controlled release properties. Journal of Controlled Release,2003,86:123-30.
[48]Shi M., Yang Y. Y., Chaw C. S., et al. Double walled POE/PLGA microspheres: encapsulation of water-soluble and water-insoluble proteins and their release properties. Journal of Controlled Release,2003,89:167-77.
[49]Zhou S., Liao X., Li X., Deng X., and Li H. Poly-D, L-lactide-co-poly(ethylene glycol) microspheres as potential vaccine delivery systems. Journal of Controlled Release,2003,86:195-205.
[50]Kanke M., Simmons G. H., Weiss D. L., Bivins B. A., and Deluca P. P. Clearance of 141Ce-labelled microspheres from blood and distribution in specific organs following intravenous and intra-arterial administration in beagle dogs. Journal of Pharmaceutical Science,1980,69:755-762.
[51]Roskos K. and Maskiewicz R. Degradable controlled release systems useful for protein delivery. In:Sanders L and Hendren R, eds. Protein delivery: Physical system. New York:Plenum,1997:45-65.
[52]Chen H. and Langer R. Oral particulate delivery:Status and future trends. Adv. Drug Del. Rev.,1998,34:339-350.
[53]Edlund U., Albertsson A. C. Degradable Polymer Microspheres for Controlled Drug Delivery. Advances in Polymer Sci.2002,157:67-112.
[54]张晟,王亚辉,张新民,熊成东,邓先模. 在药物缓释体系中应用的可生物降解材料. 合成化学,1999,7:394-399.
[55]Gopferich A. and Tessmar J. Polyanhydride degradation and erosion. Adv. Drug Del. Rev.,2002,54:911-931.
[56]Perez C., Castellanos I., Costantino H., et al. Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers. J. Pharmacy and Pharmacology,2002,54:301-313.
[57]Castellanos I. J., Cruz G., Crespo R., Griebenow K. Encapsulation-induced aggregation and loss in activity of gamma-chymotrypsin and their prevention. J. Controlled Release,2002,81(3):307-319.
[58]Al-Azzam W., Pastrana E. A., Griebenow K. Co-lyophilization of bovine serum albumin(BSA) with poly(ethylene glycol) improves efficiency of BSA encapsulation and stability in polyester microspheres by a solid-in-oil-in-oil technique. Biotechnology Letters,2002,24(16):1367-1374.
[59]Perez C., De Jesus P., Griebenow K, Preservation of lysozyme structure and function upon encapsulation and release from poly(lactic-co-glycolic) acid microspheres prepared by the water-in-oil-in-water method. International J. Pharm.,2002,248(1-2):193-206.
[60]Castellanos IJ, Crespo R, Griebenow K. Poly(ethylene glycol) as stabilizer and emulsifying agent:a novel stabilization approach preventing aggregation and inactivation of proteins upon encapsulation in bioerodible polyester microspheres. J. Controlled Release,2003,88(1):135-145.
[61]Perez-Rodriguez C, Montano N, Gonzalez K, Griebenow K. Stabilization of alpha-chymotrypsin at the CH2C12/water interface and upon water-in-oil-in-water encapsulation in PLGA microspheres. J. Controlled Release,2003,89(1):71-85.
[62]Perez C, Griebenow K. Effect of salts on lysozyme stability at the water-oilinterface and upon encapsulation in poly(lactic-co-glycolic) acid microspheres. Biotechnology and Bioengineering,2003,82(7):825-832.
[63]Burke PA, Klumb LA, Herberger JD, et al. Poly(lactide-co-glycolide) microsphere formulations of darbepoetin alfa:Spray drying is an alternative to encapsulation by spray-freeze drying. Pharm. Res.,2004,21(3):500-506.
[64]Pechenov S, Shenoy B, Yang MX, Basu SK, Margolin AL. Injectable controlled release formulations incorporating protein crystals. J. Controlled Release, 2004,96 (1):149-158.
[65]Leach WT, Simpson DT, Val TN, et al. Uniform encapsulation of stable protein nanoparticles produced by spray freezing for the reduction of burst release. J. Pharm. Sci.,2005,94 (1):56-69.
[66]Srinivasan C, Katare YK, Muthukumaran T, Panda AK. Effect of additives on encapsulation efficiency, stability and bioactivity of entrapped lysozyme from biodegradable polymer particles. J. Microencapsulation,2005,22 (2): 127-138.
[67]Al-Azzam W, Pastrana EA, King B, Mendez J, Griebenow K. Effect of the covalent modification of horseradish peroxidase with poly (ethylene glycol) onthe activity and stability upon encapsulation in polyester microspheres. J. Pharm. Sci.,2005,94 (8):1808-1819.
[68]He JT, Su HB, Li GP, et al. Stabilization and encapsulation of a staphylokinase variant (K35R) into poly (lactic-co-glycolic acid) microspheres. Int. J. Pharm.,2006,309(1-2):101-108.
[69]Zhi ZL, Haynie DT. Straightforward and effective protein encapsulation in polypeptide-based artificial cells. Artificial Cells Blood Substitutes and Biotechnology,2006,34(2):189-203.
[70]Castellanos IJ, Flores G, Griebenow K. Effect of cyclodextrins on alpha-chymotrypsin stability and loading in PLGA microspheres upon S/O/W encapsulation. J. Pharm. Sci.,2006,95 (4):849-858.
[71]Katare YK, Panda AK. Influences of excipients on in vitro release and in vivo performance of tetanus toxoid loaded polymer particles. European J. Pharm. Sci.,2006,28 (3):179-188.
[72]Maschke A, Cali N, Appel B, et al. Micronization of insulin by high pressure homogenization. Pharm. Res.,2006,23 (9):2220-2229.
[73]Gu H, Song C, Long D, et al. Controlled release of recombinant human nerve growth factor (rhNGF) from poly[(lactic acid)-co-(glycolic acid)] microspheres for the treatment of neurodegenerative disorders. Poly. International,2007,56 (10):1272-1280.
[74]Morlock M., Koll H., Winter G., Kissel T. Microencapsulation of rh-erythropoietin, using biodegradable poly(D, Llactide-co-glycolide): protein stability and the effects of stabilizing excipients. Eur. J. Pharm. Biopharm.,1997,43:29-36.
[75]Morlock M., Kissel T., Li Y. X., Koll H., Winter G. Erythropoietin loaded microspheres prepared from biodegradable LPLG-PEO-LPLG triblock copolymers: protein stabilization and in-vitro release properties. J. Control. Release, 1998,56:105-115.
[76]Crotts G., Park T. G. Protein delivery from poly(lactic-coglycolicacid) biodegradable microspheres:release kinetics and stability issues. J. Microencapsul,1998,15:699-713.
[77]Kim H. K., Park T. G. Microencapsulation of human growth hormone within biodegradable polyester microspheres:protein aggregation stability andincomplete release mechanism. Biotechnol. Bioeng.,1999,65:659-667.
[78]Sah H. Protein behavior at the water/methylene chloride interface. J. Pharm. Sci.,1999,88:1320-1325.
[79]Sah H. Protein instability toward organic solvent/water emulsication: Implications for protein microencapsulation into microspheres. PDA J. Pharm. Sci. Technol.,1999,53:3-10.
[80]Sah H. Stabilization of proteins against methylene chloride water interface-induced denaturation and aggregation. J. Control. Release,1999,58: 143-151.
[81]Van de Weert M., Hoechstetter J., Hennink W. E., Crommelin D. J. The effect of a water/organic solvent interface on the structural stability of lysozyme. J. Control. Release,2000,68:351-359.
[82]Perez C., Griebenow K. Improved activity and stability of lysozyme at the water/CH2C12 interface:enzyme unfolding and aggregation and its prevention by polyols. J. Pharm. Pharmacol.,2001,53:1217-1226.
[83]Lu W., Park T. G. Protein release from poly(lactic-co-glycolic acid) microspheres:protein stability problems. PDA J. Pharm. Sci. Technol.,1995, 49:13-19.
[84]Singh M., Shirley B., Bajwa K., et al. Controlled release of recombinant insulin-like growth factor from a novel formulation of poly lactide-co-glycolide microparticles. J. Control. Release,2001,70:21-28.
[85]Cleland J. L., Jones A. J. S. Stable formulations of recombinant human growth hormone and interferon-gamma for microencapsulation in biodegradable microspheres. Pharm. Res.,1996,13:1464-1475.
[86]Affleck R., Xu Z.F., Suzawa V., et al. Enzymatic catalysisand dynamics in low-water environments. Proc. Natl Acad. Sci. USA,1992,89:1100-1104.
[87]Griebenow K., Klibanov A.M. On protein denaturation in aqueous-organic mixtures but not in pure organic solvents. J. Am. Chem. Soc.,1996,118: 11695-11700.
[88]Barron L. D., Hecht L., Wilson G. The lubricant of life:a proposal that solvent water promotes extremely fast conformational fluctuations in mobile heteropolypeptide structure. Biochemistry,1997,36:13143-13147.
[89]Klibanov A.M. Why are enzymes less active in organic solvents than in water? Trends Biotechnol.,1997,15:97-101.
[90]Zaks A., Klibanov A.M. Enzymatic catalysis in organic media at 100℃. Science,1984,224:1249-1251.
[91]Volkin D. B., Staubli A., Langer R., Klibanov A.M. Enzyme thermoinactivation in anhydrous organic solvents. Biotechnol. Bioeng.,1991, 37:843-853.
[92]Griebenow K., Laureano Y. D., Santos A. M., et al. Improved enzyme activity and enantioselectivity in organic solvents by methyl-b-cyclodextrin. J. Am. Chem. Soc,1999,121:8157-8163.
[93]Griebenow K., Vidal M. W., Baez C., Santos A. M., Barletta G. Native-likeenzyme properties are important for optimum activity in neat organic solvents. J. Am. Chem. Soc.,2001,123:5380-5381.
[94]Santos A.M., Vidal M., Pacheco Y., et al. Effect of crown ethers on the structure, stability, activity, and enantioselectivity of subtilisin Carlsberg in organic solvents. Biotechnol. Bioeng.,2001,74:295-308.
[95]Partridge J., Moore B. D., Halling P. J. A-Chymotrypsin stability in aqueous-acetonitrile mixtures:is the native enzyme thermodynamically or kinetically stable under low water conditions? J. Mol. Catal. B-Enzymatic,1999, 6:11-20.
[96]Tobio M., Alonso M. J. Study of the inactivation process of the tetanus toxoid in contact with poly (lactic glycolic acid) degrading microspheres. Stp. Pharm. Sciences,1998,8:303-310.
[97]Tobio M., Schwendeman S. P., Guo Y., et al. Improved immunogenicity of a core-coated tetanus toroid delivery system. Vaccine,1999,18:618-622.
[98]Schwendeman S. P., Tobio M., Joworowicz M., et al. New strategies for the microencapsulation of tetanus vaccine. J. Microencapsul.,1998,15: 299-318.
[99]Lam X. M., Duenas E. T., Daugherty A. L., Levin N., Cleland J. L. Sustainedrelease of recombinant human insulin-like growth factor-Ⅰ for treatment of diabetes. J. Control. Release,2000,67:281-292.
[100]Lam X. M., Duenas E. T., Cleland J. L. Encapsulation and stabilization of nerve growth factor into poly(lactic-co-glycolic) acid microspheres. J. Pharm. Sci.,2001,90:1356-1365.
[101]Cleland J. L., Duenas E.T., Park A., et al. Development of poly(D, L lactide-co-glycolide) microsphere formulations containing recombine anthuman vascular endothelial growth factor to promote local angiogenesis. J. Control. Release,2001,72:13-24.
[102]Sherman J., Chin B., Huibers P.D.T., Garcia-Valls G., Hatton T. A. Solvent replacement for green processing. Environ. Health Perspect.,1998,106 (Suppl.1):253-271.
[103]Thomasin C., Johansen P., Adler R., et al. A contribution to overcoming theproblem of residual solvents in biodegradable microspheres prepared by coacervation. Eur. J. Pharm. Biopharm.,1996,42:16-24.
[104]Castellanos I. J., Carrasquillo K. G., De Jesus Lopez J., et al. Encapsulation of bovine serum albumin in poly(lactide-co-glycolide) microspheres by the solid-in-oil-inwater technique. J. Pharm. Pharmacol.,2001, 53:167-178.
[105]Fu K., Griebenow K., Hsieh L., et al. FTIR characterization of the secondary structure of proteins encapsulated within PLGA microspheres. J. Control. Release,1999,58:357-366.
[106]King T. W., Patrick C. W. Development and in vitro characterization of vascular endothelial growth factor (VEGF)-loaded poly(DL-lactic-co-glycolic acid)-poly(ethylene glycol) microspheres using a solid encapsulation-single emulsionsolvent-extraction technique. J. Biomed. Mater. Res.,2000,51: 383-390.
[107]Morita T., Sakamura Y., Horikiri Y., Suzuki T., Yoshino H. Protein encapsulation into biodegradable microspheres by a novel S/O/W emulsion method using poly(ethylene glycol) as a protein micronization adjuvant. J. Control. Release,2000,69:435-444.
[108]Carrasquillo K. G., Apoute Carro J. C., Alejandro A., et al. Reduction of structural perturbations in bovine serum albumin by non-aqueous microencapsulation. J. Pharm. Pharmacol.,2001,53:115-120.
[109]Carrasquillo K. G., Stanley A.M., Aponte Carro J. C., et al. Nonaqueous encapsulation of excipient-stabilized spray freeze-dried BSA into poly(lactide-co-glycolide) microspheres results in release of native protein. J.Control. Release,2001,76:199-208.
[110]Maa Y. F., Hsu C. C. Effect of primary emulsions on microsphere size and protein-loading in the double emulsion process. J. Microencapsul.,1997,14: 225-241.
[111]Costantino H.R., Firouzabadian L., Hogeland K., et al. Protein spray-freeze drying. Effect of atomization conditions on particle size and stability. Pharm.Res.,2000,17:1374-1383.
[112]Chuiko A. A., Pentyuk 0.0., and Pogorelyi V. K.. Enterosorbent Silics Properties and Clinical Application. Chemistry, Physics and Technology of Surfaces,2001, (4-6):290-300.
[113]刘付胜聪, 肖汉宁, 李玉平. 纳米SiO2表面吸附聚丙烯酰胺及其液相分散稳定性.硅酸盐学报,2004,32(7)：816-821.
[114]范浩军,石碧,段镇基.蛋白质-无机纳米杂化制备新型胶原蛋白材料.功能材料,2004,3(35)：373-382.
[115]Novak B M. A dv. Mater.,1993,5 (6):422
[116]Sanchez C, R ibot F. N ew J. Chem.,1994,18:1007-1047
[117]Schubert U, Hu β sing N, Lorenz A. Chem. M ater.1995,7:2010-2027.
[118]符连社(FU L ianshe),等.材料科学与工程(MateriSciences and Engineering),1999,17 (1):84-88
[119]LevyD, Einhorn S,V inirD. J Non2 Cryst. Solids,1989,113:137-145
[120]A nnir D, levy D, Reisfeld R. J. Phys. Chem.,1984,88:5956-5959
[121]叶辉(YE Hui),等.材料研究学报(Chinese Journal of Materials Research),1999,13 (1):68-72
[122]Landry C T J T, Coltrain B K, L andry M R. PolymPrep r.,1991,32: 514
[123]Zopp iR A, De Castro C R, Yoshida IV P, et al. Polymer 1997,38:5705-5712
[124]Goizet S, Schrot ter J C, SmaihiM, et al. New J Chem.,1997,21:461-468
[125]Novak B M, Ellsworth M, Wall ow T, et al. Polymer. Prep r.,1990, 31:698-699
[126]EllsworthM W, Novak BM. Chem. M ater.,1993,5:839-844
[127]Wen J, W ilkes G L. Chem. M ater.,1996,8:1667-1681
[128]A bboud M, Turner M, Duguet E, et al. J. M ater Chem.,1997,7:1527-1532
[129]Seckin T, Gu 0 ltek A,0 β nal Y, et al. J. M ater Chem.,1997,7: 265-269
[130]U suki A, Roj oma Y, Kawasum i M, et al. Polymer. Prep r,1987,24: 247
[131]Lan T, Kaviratna P, Pinnavaia T J. Chem. M ater,1995,7:2214-2250
[132]M esersm ith P B, Giannelis E P. Chem. M ater.,1993,5:1064-1066
[133]A randa P, Ruiz2hizky E. Chem. M ater,1992,4:1395-1403
[134]Wu J, L erner M M. Chem. M ater,1993,5:835-838
[135]Burnside S D, Giannelis E P. Chem. M ater.,1995,7:1597-1600
[136]王胜杰(WAN G Sheng2jie),等.高分子学报(A cta Polymerica Sinica), 1998, (2):129
[137]V aia R A, V ansudevan S, Kraw iec W, et al. A dv. M ater.,1995, 7 (2):154-156
[138]A nsell M A, Zeppenfeld A C, Yoshi moto K, et al. Chem. M ater.,1996, 8:591-594
[139]L i J, Jos ow icz M. Chem. M ater.,1997,9:1451-1462
[140]肖明艳,陈建敏,有机-无机杂化材料研究进展,高分子材料科学与工程.2001,5(17)：6-10
[141]Kallela I, Laine Suuronen R, et al. Osteotomy site healing following mandibular sagital split osteotomY and rigid fixation with polylactide biodegradable screws. International Journal of Oral&Maxillofacial Surgery (S0901-5027) [J].1999,28 (3):166-170.
[142]Bodde H E, J ungmger H E. Mucoadhesive polymers for the buccal delivery of peptides, Drug Safety (S0114-5916) [J].1994,40(10):233-266.
[143]X. Qiu, Z. Hong, J. Hu, L. Chen, X. Chen, X. Jing, Biomacromolecules[J], 2006,7(4):1193-1190.
[144]杨亚楠,娄玲,梁奇志,陈学思,景遐斌,生物降解聚酯包埋利福平缓释微球的制备及释放行为,高等学校化学学报[J],2004,1(25)：162-165.K.
[145]Zhang, Y. Wang, MA. Hillmyer, LF. Francis, Biomaterials[J],2004,25: 2489-2500.
[146]M. Wang, R. Joseph, W. Bonfield, Biomaterials[J],1998,19:2357-2366.
[147]王秀华等.有机-无机杂化纳米复合材料合成及性能测试,功能材料[J].(2004)增刊(35)：2955-2958.
[148]杨亚楠,蔡静,陈学思,庄秀丽,景遐斌,磺化聚乳酸／纳米Ti02有机-无机杂化材料的制备,2007年高分子年会论文集[C].
[149]李大成,周大利等,纳米Ti02的特性,四川有色金属[J],2002,03：12-18.
[150]殷海荣,武丽华,张光华,陈福,明胶-CaO-SiO2-TiO2生物活性材料的制备与研究,功能材料[J],2007,04(38)：626-632.
[151]李协吉,姚亚东等,纳米TiO2分散稳定性及降解甲醛的研究,化学研究与应用[J],2006,3(18)：276-279.
[152]杜青,胡俊丽等,水包油包固体乳化法制备蛋白药物缓释微球,高等学校化学学报[J],2006,6(29)：1262-1266.
[153]徐立新,李为立,杨慕杰,纳米TiO2表面接枝聚苯乙烯及其抗紫外老化研究[J],2007,17(65)：1917-1921.
[154]徐惠,史星伟等,水热法制备Ag/TiO2纳米复合材料及其抗菌性能.兰州理工大学学报[J],2009,4(35)：26-29.
[155]沈媛,李齐方.笼型八聚(γ-氨丙基)硅倍半氧烷盐酸盐的合成与表征.有机硅材料[J],2007,21(1)：14-17.
[156]Liu Y., Yang X., Zhang W., Zheng S. Star-shaped poly (β-caprolactone) with polyhedral oligomeric silsesquioxane core. Polymer[J],2006,47: 6814-6825.
[157]Ni Y., Zheng S. X. Supramolecular Inclusion Complexation of Polyhedral Oligomeric Silsesquioxane Capped Poly(β-caprolactone) with a-Cyclodextrin. Journal of Polymer Science Part A:Polymer Chemistry[J],2007, 45:1247-1259.
[158]Langer R. Biomaterials in drug delivery and tissue engineering:one laboratory's experience. Acc. Chem. Res.,2000,33:94-101.
[159]Wang J, Wang B. M., and Schwendeman S. P. Characterization of the initial burstrelease of a model peptide from poly (D, L-lactide-co-glycolide) microspheres. J. Control. Release,2002,82:289-307.
[160]杜青,胡俊丽等.水包油包固体乳化法制备蛋白药物缓释微球.高等学校化学学报,2009,6(29)：1262-1266.
[161]Yoshida R. Preparing impulsive Drug delivery system using gels. Adv. Drug Delivery Rev.,1993,11(112):85.
[162]朱振安,毛远青.骨科生物医用材料[J].生物骨科与临床研究,2005,6(3)：212 23.
[163]Miyazaki T, Ohtsuki C, TaniharaM. Synthesis of bioactive organic-inorganic nanohybrid for bone repair through sol-gel processing[J]. Journal of Nanoscience and Nanotechnol ogy,2003,3 (6):5112 515.
[164]Chen Q, Miyata N, Kokubo T. Bioactivity and mechanical properties of poly (di methylsiloxane)-modified calcia2silica hybrids with added titania[J]. Journal of America Ceramicas Society,2003,86 (5):8062810.
[165]Tomoki 0, Yoshiki C.Organic2inorganic polymer hybrids p repared by the sol-gel method[J]. Composite Interfaces,2005, (11):5392 566.
[166]Mark J E. Some general trends in the area of organic-Inorganic composites[J]. hybrid organic-Inorganic composites,1995.123.
[167]黄剑锋.溶胶-凝胶原理与技术[M].北京：化学工业出版社,2005.1812 214.
[168]Chakravorty D, Giri A K. Chemistry for the 21 Century, "Chemistry of Advanced Materials" [M]. London:Oxford Black Well Scientific Publication, 1993
[169]张立德,牟季美.纳米材料和纳米结构[M].北京：科学出版社,2001
[170]徐滨士,梁秀兵,马世宁等.实用纳米表面技术.中国表面工程,2001,(3)：13
[171]张万跺,乔学亮等.纳米材料的表面修饰与应用.化工进展,2004,23(10)：1067
[172]周迟骏,陈忠,许仁裕.经表面修饰的RO(OH)胶粒制备动态膜及其脱色性能.化工进展,2005,24(7)：758
[173]刘波,庄志强等.粉体的表面修饰与表面包覆方法的研究.中国陶瓷工业,2004,11(1)：50
[174]古凤才,赵竹萱,李英慧等.表面修饰二氧化锡纳米微晶的制备与表征.物理化学学报,2003,19(7)：621
[175]庄严,周群等.银粒子的表面修饰及荧光表面增强效应.光谱实验室,2005, 22(4)：881
[176]付廷明,李凤生.包覆式超细复合粒子的制备.火炸药学报,2002,(1)：33
[177]王亭杰,堤敦司,金涌.用石蜡-CO2超临界流体快速膨胀在流化床中进行细颗粒包覆.化工学报,2001,52(1)：51
[178]Diuricic B, Mcgarry D, Picketing S.The preparation of ultrafine ceria-stabilize dzirconI a particles coated with yittria. J Mater Sci Lett,1993, (12):1320
[179]闰明涛,张大余,吴刚.介孔分子筛MCM-48的室温合成与表面修饰. 无机化学学报,2005,(8)：1165
[180]Abicht H—P, Langhammer HT, Feigner K-H. The influencee of silicon on microstructure and electrical properties of La-doped BaTiO3 ceramics. [J]Mater Sci 1991,26:2337
[181]刘雨青, 郭金彦等. 聚合物乳液法表面修饰改性Fe304磁性纳米粒子特性研究.精细化工,2005,22(9)：645
[182]刘红华,邵鑫等.表面修饰FeS纳米微粒的研究——合成及表征. 润滑与密封,2005,(5)： 61
[183]徐存英,张雪苹等.表面修饰的Fe3/TiCh制备研究.云南化工,2005,32(1)：1
[184]徐存英,张鹏翔等.表面修饰的钛酸钡的拉曼光谱.物理学报,2005,54(11)： 5089
[185]Victor K Lamer, Robert H Dinegar. Theory production and echanism of formation of mono dispersed hydrosols. [J]AmChem Soc,1950,72(11):4847
[186]Aj a y K Grag, Lutgard C, De Jonghe. Micro encapsulation of silicon nitride particles with ytria and yttria-aluminaprecur—sons. [J]Mater Res,1990, 5(1):136
[187]张巨先, 候耀永, 高陇桥, 等. 非均匀成核法改性纳米SiC粉体表面研究. 硅酸盐学报,1998,26(6)：762
[188]张巨先, 高陇桥.包覆型纳米水悬浮液流变特性研究.材料科学与工程,2001,73(1)：46
[2]Brouwers JRBJ. Advanced and controlled drug delivery systems in clinical disease management. Pharmacy World & Science,1996,18:153-162.
[3]Deboer A and Breimer D. The blood-brain-barrier-clinical implications for drug-delivery to the brain. J. Roy. Coll. Phys. Lond.,1994,28:502-506.
[4]Uhrich K. E., Cannizzaro S. M., Langer R. S. Polymeric Systems for Controlled Drug Release. Chem. Rev.,1999,99:3181-3198.
[5]Jayanth P. and Vinod L. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Advanced Drug Delivery Reviews,2003,55:329-347.
[6]Dang W., Colvin 0., Brem H., et al. Covalent coupling of methotrexate to dextran enhances the penetration of cytotoxicity into a tissue-like matrix. Cancer Res.,1994,54:1729-1735.
[6]Walter K., Tamargo R., Olivi A., et al. Intratumoral chemotherapy. Neurosurgery,1995,37:1129-1145.
[7]Katayama N., Tanaka R., Ohno Y., et al. Implantable slow-release cyclosporine A (CYA) delivery system to thoracic lymph duct. Int. J. Pharm., 1995,115:87-93.
[8]Wagenaar B. and Muller B. Piroxicam release from spray-dried biodegradable microspheres. Biomaterials,1994,15:49-54.
[9]Conforti A., Bertani S., Lussignoli S., et al. Anti-inflammatory activity of polyphosphazene-based naproxen slow-release systems. J. Pharm. Pharmacol. 1996,48:468-473.
[10]Schierholz J., Rump A., and Pulverer G. New antiinfectious biomaterials-ciprofloxacin containing polyurethanes as potential drug delivery systems to prevent foreign-body infections. Drug Res.,1997,47: 70-74.
[11]Maniar M., Domb A., Haffer A., and Shah J. Controlled-release of a local-anesthetic from fatty-acid dimer based polyanhydride. J. Control. Release,1994,30:233-239.
[12]Johnson 0., Cleland J., Lee H., Charnis M., et al. A month-long effect from a single injection of microencapsulated human growth hormone. Nat. Med., 1996,2:795-799.
[13]Mcgee J., Davis S., and Ohagan D. The immunogenicity of a model protein entrapped in poly(lactide-co-glycolide) microparticles prepared by a novel phase-separation technique. J. Control. Release,1994,31:55-60.
[14]Sinha V. and Trehan A. Biodegradable microspheres for protein delivery. J. Control. Release,2003,90:261-280.
[15]Chu L. Y., Li Y., Zhu J. H., et al. Control of pore size and permeability of a glucose-responsive gating membrane for insulin delivery. J. Control. Release,2004,97:43-53.
[16]Traitel T., Cohen Y., and Kost J. Characterization of glucose-sensitive insulinrelease systems in simulated in vivo conditions. Biomaterials,2000, 21:1679-1687.
[17]李赛. 高分子纳米粒子在靶向药物载体中的研究进展. 生物医学工程学杂志,2004,21(3)：495-497.
[18]Birnbaum D., Kosmala J. Controlled release of β-estradiol from PLGA microparticles:the effect of organic phase solvent on encapsulation and realease. Journal of Controlled Release,2000,65:375.
[19]张志清,杨秀岭,樊德厚.抗癌药物白蛋白微球的研究进展.中国药师,1999,2(4)：195-197.
[20]盛洁, 山登布卡, 谢蜀生等. 单克隆抗体BDI-1导向的阿霉素白蛋白毫微球对人膀胱癌细胞的特异杀伤活性. 药学学报,1995,30(9)：706.
[21]Rihova B. Recepto-mediated targeted drug or toxin delivery. Advanced Drug Delivery Reviews,1998,29 (3):273.
[22]Yukiko N., Hiroyuki Y., Lymphatic targeting with nanoparticulate system. Advanced Drug Delivery Reviews,2001,47(1):55.
[23]Janes K.A., Calvo P., Alonso M. J. Polyaccharide colloidal particles as delivery systems for macro-molecules. Advanced Drug Delivery Reviews,2001, 47(1):83.
[24]Serizawa T., Chen M. Q., Akashl M. Graft copolymers having hydrophobic backbone and hydrophilic branches poly(strene) nanospheres with novel thermsensitive poly (N-vinylisobu-tyramide)s on their surfaces. J Polym Sci Part A:Polym Chem,1998,36:2581.
[25]Duncan R. and Spreafico F. Polymer conjugates-pharmacokinetic considerations for design and development. Clin. Pharmacokinet.,1994,27: 290-306.
[26]Langer R. New methods of drug delivery. Science,1990,249:1527-1533.
[27]Khandare J. and Minko T. Polymer-drug conjugates:Progress in polymeric prodrugs. Prog. Polym. Sci.,2006,31:359-397.
[28]David A., Kopeckova P., Minko T., et al. Design of a multivalent galactoside ligand for selective targeting of hpma copolymer-doxorubicin conjugates to human colon cancer cells. Eur. J. Cancer,2004,40:148-157.
[29] Satchi-Fainaro R., Wrasidlo W., Lode H., and Shabat D. Synthesis and characterization of a catalytic antibody-HPMA copolymerconjugate as a tool for tumor selective prodrug activation. Bioorg. Med. Chem.,2002,10:3023-3029.
[30]Wichterle 0. and Lim D. Hydrophilic gels in biologic use. Nature,1960, 185:117-118.
[31]Park K., Shalaby W. S. W., and Park H. Biodegradable hydrogels for drug delivery. PA:Lancaster,1993.
[32]Hoffman A. S., Schmer G., Harris C., and Kraft W. G. Covalent binding of biomolecules to radiation-grafted hydrogels on inert polymer surfaces. Trans. Am. Soc. Artif. Intern. Organs,1972,18:10-18.
[33]Harland R. S. and Prudhomme R. K. Polyelectrolyte gels:Properties, preparation, and applications. Washington D C:American Chemical Society,1992.
[34]Kamath K. and Park K. Biodegradable hydrogels in drug delivery. Advanced Drug Delivery Reviews,1993,11(1-2):59-84.
[35]Campoccia D., Doherty P., Radice M., et al. Semisynthetic resorbable materials from hyaluronan esterification. Biomaterials,1998,19:2101-27.
[36]Prestwich G. D., Marecak D. M., Marecak J. F., Verpenetracruysse K. P., and Ziebell M. R. Controlled chemical modification of hyaluronic acid. Journal of Controlled Release,1998,53:93-103.
[37]Hennink W. E. and Nostrum C. F.V. Novel crosslinking methods to design hydrogels. Adv. Drug Del. Rev,2002,54:13-36.
[38]Park K. and Park H. Smart Hydrogels. In:J.C. Salamone (Ed.), Concise Polymeric Materials Encyclopedia, CRC Press, Boca Raton,1999, pp.1476-8.
[39]Qiu Y. and Park K. Environment-sensitive hydrogels for drug delivery. Adv. Drug Del. Rev.,2001,53:321-339.
[40]Gupta P., Vermani K., and Garg S.. Hydrogels:From controlled release to pH-responsive drug delivery. Drug Discov. Today,2002,7:569-579.
[41]Lowman A.M. and Peppas N. A. Hydrogels, in Encyclopaedia of controlled drug delivery, E Mathiowitz, Ed. John Wiley & Sons.1999,397-418.
[42]Kost J. Intelligent drug delivery systems, in Encyclopaedia of controlled drugdelivery, E Mathiowitz, Edi. John Wiley & Sons.1999,445-459.
[43]Ishihara K., Kobayashi M., Ishimaru N., and Shinohara I. Glucose induced permeation control of insulin through a complex membrane consisting of immobilized glucose oxidase and a poly(amine). Polym. J.,1984,16:625-631.
[44]Ishihara K. and Matsui K. Glucose-responsive insulin release from polymer capsule. J. Polym. Sci. Polym. Lett. Ed.,1986,24:413-417.
[45]Allemann E., Gurny R., Doelker E., et al. Distribution, kinetics and elimination of radioactivity after intravenous and intramuscular injection of 14C-savoxepine loaded poly(L-lactic acid) nanospheres to rats. Journal of Controlled Release 1994,29(1-2):97-104.
[46]Mu L. and Feng S. S. A novel controlled release formulation for the anticancer drug paclitaxel (Taxol(?)):PLGA nanoparticles containing vitamin E TPGS. Journal of Controlled Release,2003,86:33-48.
[47]Barrio G. G., Novo F. J., and Irache J. M. Loading of plasmid DNA into PLGA microparticles using TROMS (Total Recirculation One-Machine System): evaluation of its integrity and controlled release properties. Journal of Controlled Release,2003,86:123-30.
[48]Shi M., Yang Y. Y., Chaw C. S., et al. Double walled POE/PLGA microspheres: encapsulation of water-soluble and water-insoluble proteins and their release properties. Journal of Controlled Release,2003,89:167-77.
[49]Zhou S., Liao X., Li X., Deng X., and Li H. Poly-D, L-lactide-co-poly(ethylene glycol) microspheres as potential vaccine delivery systems. Journal of Controlled Release,2003,86:195-205.
[50]Kanke M., Simmons G. H., Weiss D. L., Bivins B. A., and Deluca P. P. Clearance of 141Ce-labelled microspheres from blood and distribution in specific organs following intravenous and intra-arterial administration in beagle dogs. Journal of Pharmaceutical Science,1980,69:755-762.
[51]Roskos K. and Maskiewicz R. Degradable controlled release systems useful for protein delivery. In:Sanders L and Hendren R, eds. Protein delivery: Physical system. New York:Plenum,1997:45-65.
[52]Chen H. and Langer R. Oral particulate delivery:Status and future trends. Adv. Drug Del. Rev.,1998,34:339-350.
[53]Edlund U., Albertsson A. C. Degradable Polymer Microspheres for Controlled Drug Delivery. Advances in Polymer Sci.2002,157:67-112.
[54]张晟,王亚辉,张新民,熊成东,邓先模. 在药物缓释体系中应用的可生物降解材料. 合成化学,1999,7:394-399.
[55]Gopferich A. and Tessmar J. Polyanhydride degradation and erosion. Adv. Drug Del. Rev.,2002,54:911-931.
[56]Perez C., Castellanos I., Costantino H., et al. Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers. J. Pharmacy and Pharmacology,2002,54:301-313.
[57]Castellanos I. J., Cruz G., Crespo R., Griebenow K. Encapsulation-induced aggregation and loss in activity of gamma-chymotrypsin and their prevention. J. Controlled Release,2002,81(3):307-319.
[58]Al-Azzam W., Pastrana E. A., Griebenow K. Co-lyophilization of bovine serum albumin(BSA) with poly(ethylene glycol) improves efficiency of BSA encapsulation and stability in polyester microspheres by a solid-in-oil-in-oil technique. Biotechnology Letters,2002,24(16):1367-1374.
[59]Perez C., De Jesus P., Griebenow K, Preservation of lysozyme structure and function upon encapsulation and release from poly(lactic-co-glycolic) acid microspheres prepared by the water-in-oil-in-water method. International J. Pharm.,2002,248(1-2):193-206.
[60]Castellanos IJ, Crespo R, Griebenow K. Poly(ethylene glycol) as stabilizer and emulsifying agent:a novel stabilization approach preventing aggregation and inactivation of proteins upon encapsulation in bioerodible polyester microspheres. J. Controlled Release,2003,88(1):135-145.
[61]Perez-Rodriguez C, Montano N, Gonzalez K, Griebenow K. Stabilization of alpha-chymotrypsin at the CH2C12/water interface and upon water-in-oil-in-water encapsulation in PLGA microspheres. J. Controlled Release,2003,89(1):71-85.
[62]Perez C, Griebenow K. Effect of salts on lysozyme stability at the water-oilinterface and upon encapsulation in poly(lactic-co-glycolic) acid microspheres. Biotechnology and Bioengineering,2003,82(7):825-832.
[63]Burke PA, Klumb LA, Herberger JD, et al. Poly(lactide-co-glycolide) microsphere formulations of darbepoetin alfa:Spray drying is an alternative to encapsulation by spray-freeze drying. Pharm. Res.,2004,21(3):500-506.
[64]Pechenov S, Shenoy B, Yang MX, Basu SK, Margolin AL. Injectable controlled release formulations incorporating protein crystals. J. Controlled Release, 2004,96 (1):149-158.
[65]Leach WT, Simpson DT, Val TN, et al. Uniform encapsulation of stable protein nanoparticles produced by spray freezing for the reduction of burst release. J. Pharm. Sci.,2005,94 (1):56-69.
[66]Srinivasan C, Katare YK, Muthukumaran T, Panda AK. Effect of additives on encapsulation efficiency, stability and bioactivity of entrapped lysozyme from biodegradable polymer particles. J. Microencapsulation,2005,22 (2): 127-138.
[67]Al-Azzam W, Pastrana EA, King B, Mendez J, Griebenow K. Effect of the covalent modification of horseradish peroxidase with poly (ethylene glycol) onthe activity and stability upon encapsulation in polyester microspheres. J. Pharm. Sci.,2005,94 (8):1808-1819.
[68]He JT, Su HB, Li GP, et al. Stabilization and encapsulation of a staphylokinase variant (K35R) into poly (lactic-co-glycolic acid) microspheres. Int. J. Pharm.,2006,309(1-2):101-108.
[69]Zhi ZL, Haynie DT. Straightforward and effective protein encapsulation in polypeptide-based artificial cells. Artificial Cells Blood Substitutes and Biotechnology,2006,34(2):189-203.
[70]Castellanos IJ, Flores G, Griebenow K. Effect of cyclodextrins on alpha-chymotrypsin stability and loading in PLGA microspheres upon S/O/W encapsulation. J. Pharm. Sci.,2006,95 (4):849-858.
[71]Katare YK, Panda AK. Influences of excipients on in vitro release and in vivo performance of tetanus toxoid loaded polymer particles. European J. Pharm. Sci.,2006,28 (3):179-188.
[72]Maschke A, Cali N, Appel B, et al. Micronization of insulin by high pressure homogenization. Pharm. Res.,2006,23 (9):2220-2229.
[73]Gu H, Song C, Long D, et al. Controlled release of recombinant human nerve growth factor (rhNGF) from poly[(lactic acid)-co-(glycolic acid)] microspheres for the treatment of neurodegenerative disorders. Poly. International,2007,56 (10):1272-1280.
[74]Morlock M., Koll H., Winter G., Kissel T. Microencapsulation of rh-erythropoietin, using biodegradable poly(D, Llactide-co-glycolide): protein stability and the effects of stabilizing excipients. Eur. J. Pharm. Biopharm.,1997,43:29-36.
[75]Morlock M., Kissel T., Li Y. X., Koll H., Winter G. Erythropoietin loaded microspheres prepared from biodegradable LPLG-PEO-LPLG triblock copolymers: protein stabilization and in-vitro release properties. J. Control. Release, 1998,56:105-115.
[76]Crotts G., Park T. G. Protein delivery from poly(lactic-coglycolicacid) biodegradable microspheres:release kinetics and stability issues. J. Microencapsul,1998,15:699-713.
[77]Kim H. K., Park T. G. Microencapsulation of human growth hormone within biodegradable polyester microspheres:protein aggregation stability andincomplete release mechanism. Biotechnol. Bioeng.,1999,65:659-667.
[78]Sah H. Protein behavior at the water/methylene chloride interface. J. Pharm. Sci.,1999,88:1320-1325.
[79]Sah H. Protein instability toward organic solvent/water emulsication: Implications for protein microencapsulation into microspheres. PDA J. Pharm. Sci. Technol.,1999,53:3-10.
[80]Sah H. Stabilization of proteins against methylene chloride water interface-induced denaturation and aggregation. J. Control. Release,1999,58: 143-151.
[81]Van de Weert M., Hoechstetter J., Hennink W. E., Crommelin D. J. The effect of a water/organic solvent interface on the structural stability of lysozyme. J. Control. Release,2000,68:351-359.
[82]Perez C., Griebenow K. Improved activity and stability of lysozyme at the water/CH2C12 interface:enzyme unfolding and aggregation and its prevention by polyols. J. Pharm. Pharmacol.,2001,53:1217-1226.
[83]Lu W., Park T. G. Protein release from poly(lactic-co-glycolic acid) microspheres:protein stability problems. PDA J. Pharm. Sci. Technol.,1995, 49:13-19.
[84]Singh M., Shirley B., Bajwa K., et al. Controlled release of recombinant insulin-like growth factor from a novel formulation of poly lactide-co-glycolide microparticles. J. Control. Release,2001,70:21-28.
[85]Cleland J. L., Jones A. J. S. Stable formulations of recombinant human growth hormone and interferon-gamma for microencapsulation in biodegradable microspheres. Pharm. Res.,1996,13:1464-1475.
[86]Affleck R., Xu Z.F., Suzawa V., et al. Enzymatic catalysisand dynamics in low-water environments. Proc. Natl Acad. Sci. USA,1992,89:1100-1104.
[87]Griebenow K., Klibanov A.M. On protein denaturation in aqueous-organic mixtures but not in pure organic solvents. J. Am. Chem. Soc.,1996,118: 11695-11700.
[88]Barron L. D., Hecht L., Wilson G. The lubricant of life:a proposal that solvent water promotes extremely fast conformational fluctuations in mobile heteropolypeptide structure. Biochemistry,1997,36:13143-13147.
[89]Klibanov A.M. Why are enzymes less active in organic solvents than in water? Trends Biotechnol.,1997,15:97-101.
[90]Zaks A., Klibanov A.M. Enzymatic catalysis in organic media at 100℃. Science,1984,224:1249-1251.
[91]Volkin D. B., Staubli A., Langer R., Klibanov A.M. Enzyme thermoinactivation in anhydrous organic solvents. Biotechnol. Bioeng.,1991, 37:843-853.
[92]Griebenow K., Laureano Y. D., Santos A. M., et al. Improved enzyme activity and enantioselectivity in organic solvents by methyl-b-cyclodextrin. J. Am. Chem. Soc,1999,121:8157-8163.
[93]Griebenow K., Vidal M. W., Baez C., Santos A. M., Barletta G. Native-likeenzyme properties are important for optimum activity in neat organic solvents. J. Am. Chem. Soc.,2001,123:5380-5381.
[94]Santos A.M., Vidal M., Pacheco Y., et al. Effect of crown ethers on the structure, stability, activity, and enantioselectivity of subtilisin Carlsberg in organic solvents. Biotechnol. Bioeng.,2001,74:295-308.
[95]Partridge J., Moore B. D., Halling P. J. A-Chymotrypsin stability in aqueous-acetonitrile mixtures:is the native enzyme thermodynamically or kinetically stable under low water conditions? J. Mol. Catal. B-Enzymatic,1999, 6:11-20.
[96]Tobio M., Alonso M. J. Study of the inactivation process of the tetanus toxoid in contact with poly (lactic glycolic acid) degrading microspheres. Stp. Pharm. Sciences,1998,8:303-310.
[97]Tobio M., Schwendeman S. P., Guo Y., et al. Improved immunogenicity of a core-coated tetanus toroid delivery system. Vaccine,1999,18:618-622.
[98]Schwendeman S. P., Tobio M., Joworowicz M., et al. New strategies for the microencapsulation of tetanus vaccine. J. Microencapsul.,1998,15: 299-318.
[99]Lam X. M., Duenas E. T., Daugherty A. L., Levin N., Cleland J. L. Sustainedrelease of recombinant human insulin-like growth factor-Ⅰ for treatment of diabetes. J. Control. Release,2000,67:281-292.
[100]Lam X. M., Duenas E. T., Cleland J. L. Encapsulation and stabilization of nerve growth factor into poly(lactic-co-glycolic) acid microspheres. J. Pharm. Sci.,2001,90:1356-1365.
[101]Cleland J. L., Duenas E.T., Park A., et al. Development of poly(D, L lactide-co-glycolide) microsphere formulations containing recombine anthuman vascular endothelial growth factor to promote local angiogenesis. J. Control. Release,2001,72:13-24.
[102]Sherman J., Chin B., Huibers P.D.T., Garcia-Valls G., Hatton T. A. Solvent replacement for green processing. Environ. Health Perspect.,1998,106 (Suppl.1):253-271.
[103]Thomasin C., Johansen P., Adler R., et al. A contribution to overcoming theproblem of residual solvents in biodegradable microspheres prepared by coacervation. Eur. J. Pharm. Biopharm.,1996,42:16-24.
[104]Castellanos I. J., Carrasquillo K. G., De Jesus Lopez J., et al. Encapsulation of bovine serum albumin in poly(lactide-co-glycolide) microspheres by the solid-in-oil-inwater technique. J. Pharm. Pharmacol.,2001, 53:167-178.
[105]Fu K., Griebenow K., Hsieh L., et al. FTIR characterization of the secondary structure of proteins encapsulated within PLGA microspheres. J. Control. Release,1999,58:357-366.
[106]King T. W., Patrick C. W. Development and in vitro characterization of vascular endothelial growth factor (VEGF)-loaded poly(DL-lactic-co-glycolic acid)-poly(ethylene glycol) microspheres using a solid encapsulation-single emulsionsolvent-extraction technique. J. Biomed. Mater. Res.,2000,51: 383-390.
[107]Morita T., Sakamura Y., Horikiri Y., Suzuki T., Yoshino H. Protein encapsulation into biodegradable microspheres by a novel S/O/W emulsion method using poly(ethylene glycol) as a protein micronization adjuvant. J. Control. Release,2000,69:435-444.
[108]Carrasquillo K. G., Apoute Carro J. C., Alejandro A., et al. Reduction of structural perturbations in bovine serum albumin by non-aqueous microencapsulation. J. Pharm. Pharmacol.,2001,53:115-120.
[109]Carrasquillo K. G., Stanley A.M., Aponte Carro J. C., et al. Nonaqueous encapsulation of excipient-stabilized spray freeze-dried BSA into poly(lactide-co-glycolide) microspheres results in release of native protein. J.Control. Release,2001,76:199-208.
[110]Maa Y. F., Hsu C. C. Effect of primary emulsions on microsphere size and protein-loading in the double emulsion process. J. Microencapsul.,1997,14: 225-241.
[111]Costantino H.R., Firouzabadian L., Hogeland K., et al. Protein spray-freeze drying. Effect of atomization conditions on particle size and stability. Pharm.Res.,2000,17:1374-1383.
[112]Chuiko A. A., Pentyuk 0.0., and Pogorelyi V. K.. Enterosorbent Silics Properties and Clinical Application. Chemistry, Physics and Technology of Surfaces,2001, (4-6):290-300.
[113]刘付胜聪, 肖汉宁, 李玉平. 纳米SiO2表面吸附聚丙烯酰胺及其液相分散稳定性.硅酸盐学报,2004,32(7)：816-821.
[114]范浩军,石碧,段镇基.蛋白质-无机纳米杂化制备新型胶原蛋白材料.功能材料,2004,3(35)：373-382.
[115]Novak B M. A dv. Mater.,1993,5 (6):422
[116]Sanchez C, R ibot F. N ew J. Chem.,1994,18:1007-1047
[117]Schubert U, Hu β sing N, Lorenz A. Chem. M ater.1995,7:2010-2027.
[118]符连社(FU L ianshe),等.材料科学与工程(MateriSciences and Engineering),1999,17 (1):84-88
[119]LevyD, Einhorn S,V inirD. J Non2 Cryst. Solids,1989,113:137-145
[120]A nnir D, levy D, Reisfeld R. J. Phys. Chem.,1984,88:5956-5959
[121]叶辉(YE Hui),等.材料研究学报(Chinese Journal of Materials Research),1999,13 (1):68-72
[122]Landry C T J T, Coltrain B K, L andry M R. PolymPrep r.,1991,32: 514
[123]Zopp iR A, De Castro C R, Yoshida IV P, et al. Polymer 1997,38:5705-5712
[124]Goizet S, Schrot ter J C, SmaihiM, et al. New J Chem.,1997,21:461-468
[125]Novak B M, Ellsworth M, Wall ow T, et al. Polymer. Prep r.,1990, 31:698-699
[126]EllsworthM W, Novak BM. Chem. M ater.,1993,5:839-844
[127]Wen J, W ilkes G L. Chem. M ater.,1996,8:1667-1681
[128]A bboud M, Turner M, Duguet E, et al. J. M ater Chem.,1997,7:1527-1532
[129]Seckin T, Gu 0 ltek A,0 β nal Y, et al. J. M ater Chem.,1997,7: 265-269
[130]U suki A, Roj oma Y, Kawasum i M, et al. Polymer. Prep r,1987,24: 247
[131]Lan T, Kaviratna P, Pinnavaia T J. Chem. M ater,1995,7:2214-2250
[132]M esersm ith P B, Giannelis E P. Chem. M ater.,1993,5:1064-1066
[133]A randa P, Ruiz2hizky E. Chem. M ater,1992,4:1395-1403
[134]Wu J, L erner M M. Chem. M ater,1993,5:835-838
[135]Burnside S D, Giannelis E P. Chem. M ater.,1995,7:1597-1600
[136]王胜杰(WAN G Sheng2jie),等.高分子学报(A cta Polymerica Sinica), 1998, (2):129
[137]V aia R A, V ansudevan S, Kraw iec W, et al. A dv. M ater.,1995, 7 (2):154-156
[138]A nsell M A, Zeppenfeld A C, Yoshi moto K, et al. Chem. M ater.,1996, 8:591-594
[139]L i J, Jos ow icz M. Chem. M ater.,1997,9:1451-1462
[140]肖明艳,陈建敏,有机-无机杂化材料研究进展,高分子材料科学与工程.2001,5(17)：6-10
[141]Kallela I, Laine Suuronen R, et al. Osteotomy site healing following mandibular sagital split osteotomY and rigid fixation with polylactide biodegradable screws. International Journal of Oral&Maxillofacial Surgery (S0901-5027) [J].1999,28 (3):166-170.
[142]Bodde H E, J ungmger H E. Mucoadhesive polymers for the buccal delivery of peptides, Drug Safety (S0114-5916) [J].1994,40(10):233-266.
[143]X. Qiu, Z. Hong, J. Hu, L. Chen, X. Chen, X. Jing, Biomacromolecules[J], 2006,7(4):1193-1190.
[144]杨亚楠,娄玲,梁奇志,陈学思,景遐斌,生物降解聚酯包埋利福平缓释微球的制备及释放行为,高等学校化学学报[J],2004,1(25)：162-165.K.
[145]Zhang, Y. Wang, MA. Hillmyer, LF. Francis, Biomaterials[J],2004,25: 2489-2500.
[146]M. Wang, R. Joseph, W. Bonfield, Biomaterials[J],1998,19:2357-2366.
[147]王秀华等.有机-无机杂化纳米复合材料合成及性能测试,功能材料[J].(2004)增刊(35)：2955-2958.
[148]杨亚楠,蔡静,陈学思,庄秀丽,景遐斌,磺化聚乳酸／纳米Ti02有机-无机杂化材料的制备,2007年高分子年会论文集[C].
[149]李大成,周大利等,纳米Ti02的特性,四川有色金属[J],2002,03：12-18.
[150]殷海荣,武丽华,张光华,陈福,明胶-CaO-SiO2-TiO2生物活性材料的制备与研究,功能材料[J],2007,04(38)：626-632.
[151]李协吉,姚亚东等,纳米TiO2分散稳定性及降解甲醛的研究,化学研究与应用[J],2006,3(18)：276-279.
[152]杜青,胡俊丽等,水包油包固体乳化法制备蛋白药物缓释微球,高等学校化学学报[J],2006,6(29)：1262-1266.
[153]徐立新,李为立,杨慕杰,纳米TiO2表面接枝聚苯乙烯及其抗紫外老化研究[J],2007,17(65)：1917-1921.
[154]徐惠,史星伟等,水热法制备Ag/TiO2纳米复合材料及其抗菌性能.兰州理工大学学报[J],2009,4(35)：26-29.
[155]沈媛,李齐方.笼型八聚(γ-氨丙基)硅倍半氧烷盐酸盐的合成与表征.有机硅材料[J],2007,21(1)：14-17.
[156]Liu Y., Yang X., Zhang W., Zheng S. Star-shaped poly (β-caprolactone) with polyhedral oligomeric silsesquioxane core. Polymer[J],2006,47: 6814-6825.
[157]Ni Y., Zheng S. X. Supramolecular Inclusion Complexation of Polyhedral Oligomeric Silsesquioxane Capped Poly(β-caprolactone) with a-Cyclodextrin. Journal of Polymer Science Part A:Polymer Chemistry[J],2007, 45:1247-1259.
[158]Langer R. Biomaterials in drug delivery and tissue engineering:one laboratory's experience. Acc. Chem. Res.,2000,33:94-101.
[159]Wang J, Wang B. M., and Schwendeman S. P. Characterization of the initial burstrelease of a model peptide from poly (D, L-lactide-co-glycolide) microspheres. J. Control. Release,2002,82:289-307.
[160]杜青,胡俊丽等.水包油包固体乳化法制备蛋白药物缓释微球.高等学校化学学报,2009,6(29)：1262-1266.
[161]Yoshida R. Preparing impulsive Drug delivery system using gels. Adv. Drug Delivery Rev.,1993,11(112):85.
[162]朱振安,毛远青.骨科生物医用材料[J].生物骨科与临床研究,2005,6(3)：212 23.
[163]Miyazaki T, Ohtsuki C, TaniharaM. Synthesis of bioactive organic-inorganic nanohybrid for bone repair through sol-gel processing[J]. Journal of Nanoscience and Nanotechnol ogy,2003,3 (6):5112 515.
[164]Chen Q, Miyata N, Kokubo T. Bioactivity and mechanical properties of poly (di methylsiloxane)-modified calcia2silica hybrids with added titania[J]. Journal of America Ceramicas Society,2003,86 (5):8062810.
[165]Tomoki 0, Yoshiki C.Organic2inorganic polymer hybrids p repared by the sol-gel method[J]. Composite Interfaces,2005, (11):5392 566.
[166]Mark J E. Some general trends in the area of organic-Inorganic composites[J]. hybrid organic-Inorganic composites,1995.123.
[167]黄剑锋.溶胶-凝胶原理与技术[M].北京：化学工业出版社,2005.1812 214.
[168]Chakravorty D, Giri A K. Chemistry for the 21 Century, "Chemistry of Advanced Materials" [M]. London:Oxford Black Well Scientific Publication, 1993
[169]张立德,牟季美.纳米材料和纳米结构[M].北京：科学出版社,2001
[170]徐滨士,梁秀兵,马世宁等.实用纳米表面技术.中国表面工程,2001,(3)：13
[171]张万跺,乔学亮等.纳米材料的表面修饰与应用.化工进展,2004,23(10)：1067
[172]周迟骏,陈忠,许仁裕.经表面修饰的RO(OH)胶粒制备动态膜及其脱色性能.化工进展,2005,24(7)：758
[173]刘波,庄志强等.粉体的表面修饰与表面包覆方法的研究.中国陶瓷工业,2004,11(1)：50
[174]古凤才,赵竹萱,李英慧等.表面修饰二氧化锡纳米微晶的制备与表征.物理化学学报,2003,19(7)：621
[175]庄严,周群等.银粒子的表面修饰及荧光表面增强效应.光谱实验室,2005, 22(4)：881
[176]付廷明,李凤生.包覆式超细复合粒子的制备.火炸药学报,2002,(1)：33
[177]王亭杰,堤敦司,金涌.用石蜡-CO2超临界流体快速膨胀在流化床中进行细颗粒包覆.化工学报,2001,52(1)：51
[178]Diuricic B, Mcgarry D, Picketing S.The preparation of ultrafine ceria-stabilize dzirconI a particles coated with yittria. J Mater Sci Lett,1993, (12):1320
[179]闰明涛,张大余,吴刚.介孔分子筛MCM-48的室温合成与表面修饰. 无机化学学报,2005,(8)：1165
[180]Abicht H—P, Langhammer HT, Feigner K-H. The influencee of silicon on microstructure and electrical properties of La-doped BaTiO3 ceramics. [J]Mater Sci 1991,26:2337
[181]刘雨青, 郭金彦等. 聚合物乳液法表面修饰改性Fe304磁性纳米粒子特性研究.精细化工,2005,22(9)：645
[182]刘红华,邵鑫等.表面修饰FeS纳米微粒的研究——合成及表征. 润滑与密封,2005,(5)： 61
[183]徐存英,张雪苹等.表面修饰的Fe3/TiCh制备研究.云南化工,2005,32(1)：1
[184]徐存英,张鹏翔等.表面修饰的钛酸钡的拉曼光谱.物理学报,2005,54(11)： 5089
[185]Victor K Lamer, Robert H Dinegar. Theory production and echanism of formation of mono dispersed hydrosols. [J]AmChem Soc,1950,72(11):4847
[186]Aj a y K Grag, Lutgard C, De Jonghe. Micro encapsulation of silicon nitride particles with ytria and yttria-aluminaprecur—sons. [J]Mater Res,1990, 5(1):136
[187]张巨先, 候耀永, 高陇桥, 等. 非均匀成核法改性纳米SiC粉体表面研究. 硅酸盐学报,1998,26(6)：762
[188]张巨先, 高陇桥.包覆型纳米水悬浮液流变特性研究.材料科学与工程,2001,73(1)：46