聚合物胶束载药量影响因素的研究进展
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摘要
聚合物胶束是难溶性药物及DNA类大分子药物的最具潜力的递送载体之一。除生物相容性和渗透性良好、结构稳定等优势之外,它的载药量能满足临床需求。考察聚合物胶束载药量的影响因素是发挥这类运载系统临床价值的重要研究内容,聚合物组成、药物与聚合物疏水段的相容性、胶束制备方法、溶剂、温度和投药量等均可能影响聚合物胶束的载药。本文综述了聚合物胶束载药量的影响因素,分析各因素对聚合物胶束载药量的影响规律,为聚合物胶束的制备工艺优化及应用提供参考。
As one of the most promising delivery carriers of insoluble drugs and DNA, polymer micelles have unique advantages, such as high drug loading, good biocompatibility and stable structure. So its application has been widely concerned. The higher drug loading of polymer micelles can meet the needs of high dose of drugs in clinic. The factors influencing the drug loading are mainly the composition of the polymer, the compatibility of the drug with the hydrophobic segment, the preparation method of the polymeric micelles, as well as the solvent, temperature and mass ratio during the preparation process. In this paper, the influence factors of drug loading in polymer micelles are reviewed, and the regular patterns of various factors on the drug loading are briefly analyzed, which would provide reference for controlling the drug loading of polymer micelles.
As one of the most promising delivery carriers of insoluble drugs and DNA, polymer micelles have unique advantages, such as high drug loading, good biocompatibility and stable structure. So its application has been widely concerned. The higher drug loading of polymer micelles can meet the needs of high dose of drugs in clinic. The factors influencing the drug loading are mainly the composition of the polymer, the compatibility of the drug with the hydrophobic segment, the preparation method of the polymeric micelles, as well as the solvent, temperature and mass ratio during the preparation process. In this paper, the influence factors of drug loading in polymer micelles are reviewed, and the regular patterns of various factors on the drug loading are briefly analyzed, which would provide reference for controlling the drug loading of polymer micelles.
引文
[1]Yu N,Li G,Gao Y,et al.Thermo-sensitive complex micelles from sodium alginate-graft-poly(N-isopropylacrylamide)for drug release[J].Int J Biol Macromol,2016,86:296—301.
[2]Huang R,Xiang L,Liu Y,et al.Synthesis and in vitro evaluation of p H-sensitive PEG-I-d C16 block polymer micelles foranticancer drug delivery[J].JPharm Pharmacol,2016,68(6):751—761.
[3]Sun T,Li P,Oh JK.Dual location dual reduction/photoresponsive block copolymer micelles:disassembly and synergistic release[J].Macromol Rapid Commun,2015,36(19):1742—1748.
[4]Wang M,Hu H,Sun Y,et al.A pH-sensitive gene delivery system based on folic acid-PEG-chitosan-PAMAM-plasmid DNA complexes for cancer cell targeting[J].Biomaterials,2013,34(38):10120—10132.
[5]郑毅.抗人CD40单克隆抗体免疫纳米载药胶束的制备及其生物学特性的研究[D].苏州:苏州大学硕士学位论文,2013.
[6]Yu J,Li Z,Wang W,et al.Anticancer 20(R)-dammarane-3b,12b,20,25-tetrol-loaded polymeric micelles:Preparation,quantification and pharmacokinetics[J].J Chromatogr B Analyt Technol Biomed Life Sci,2016,1022:13—20.
[7]Perrut M,Jung J,Leboeuf F.Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fl uid processes.Part I:Micronization of neat particles[J].Int J Pharm,2005,288(1):3—10.
[8]Xiong XB,UludaeH,Lavasanifar A.Virus-mimetic polymeric micelles for targeted si RNA delivery[J].Biomaterials,2010,31(22):5886—5893.
[9]Li X,Li P,Zhang Y,et al.Novel mixed polymeric micelles for enhancing delivery of anticancer drug and overcoming multidrug resistance in tumor cell lines simultaneously[J].Pharm Res,2010,27(8):1498—1511.
[10]He Z,Wan X,Schulz A,et al.A high capacity polymeric micelle of paclitaxel:Implication of high dose drug therapy to safety and in vivo anti-cancer activity[J].Biomaterials,2016,101:296—309.
[11]Isoda K,Kanayama N,Fujita M,et al.DNA terminal mismatch-induced stabilization of polymer micelles from RAFT-generated poly(N-isopropylacrylamide)-DNA block copolymers[J].Chem Asian J,2013,8(12):3079—3084.
[12]Zhou W,Li C,Wang Z,et al.Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement[J].J Nanopart Res,2016,18(9):275.
[13]王狄狮,周艳霞,李承洧,等.p H敏感聚合物胶束给药系统的研究进展[J].中国新药杂志,2016,25(19):2218—2224.
[14]Gothwal A,Khan I,Gupta U.Polymeric micelles:recent advancements in the delivery of anticancer drugs[J].Pharm Res,2016,33(1):18—39.
[15]Le Garrec D,Gori S,Luo L,et al.Poly(N-vinylpyrrolidone)-block-poly(D,L-lactide)as a new polymeric solubilizer for hydrophobic anticancer drugs:in vitro and in vivo evaluation[J].J Control Release,2004,99(1):83—101.
[16]Wu WC,Chang HH.Fluorescent polymeric micelles containing fluorenederivatives formonitoring drug encapsulation and release[J].Colloid Polym Sci,2015,293(2):453—462.
[17]Li J,Li Z,Li M,et al.Synergistic effect and drug-resistance relief of paclitaxel and cisplatin caused by co-delivery using polymeric micelles[J].J Appl Polym Sci,2015,132(6):41440—41448.
[18]Wang Y,Zhu DD,Zhou J,et al.Mesoscopic simulation studies on the formation mechanis mof drugloaded polymeric micelles[J].Colloids Surf B:Biointerfaces,2015,136:536—544.
[19]Shi J,Zhang J,Shen Y,et al.Arginine-stabilized m PEGP DLLA(50/50)polymericmicelles of docetaxel by electrostatic mechanism for tumor-targeted delivery[J].Drug Deliv,2015,22(2):168—181.
[20]Vekariya RL,Ray D,Aswal VK,et al.Effect of ionic liquids on microstructures of micellar aggregates formed by PEOPPO-PEO block copolymer in aqueous solution[J].Colloids Surf A Physicochem Eng Asp,2014,462:153—161.
[21]Ali R,Farah A,Binkhathlan Z.Development and characterization of methoxy poly(ethylene oxide)-blockpoly(e-caprolactone)(PEO-b-PCL)micelles as vehicles for the solubilization and delivery of tacrolimus[J].Saudi Pharm J,2017,25(2):258—265.
[22]Gao Y,Li Y,Li Y,et al.PSMA-mediated endosome escapeaccelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular traffi cking[J].Nanoscale,2015,7(2):597—612.
[23]Li J,Zhou Y,Li C,et al.Poly(2-ethyl-2-oxazoline)-doxorubicin conjugate-based dual endosomal p H-sensitive micelles with enhanced antitumor efficacy[J].Bioconjug Chem,2015,26(1):110—119.
[24]Jiang C,Wang H,Zhang X,et al.Deoxycholic acid-modifi ed chitooligosaccharide/m PEG-PDLLA mixed micelles loaded with paclitaxel for enhanced antitumor efficacy[J].Int J Pharm,2014,475(1-2):60—68.
[25]Singh RP,Sharma G,Sonali,et al.Transferrin receptor targeted PLA-TPGS micelles improved effi cacy and safety in docetaxel delivery[J].Int J Biol Macromol,2016,83:335—344.
[26]Hu X,Yang FF,Liu CY,et al.In vitro uptake and transport studies of PEG-PLGA polymeric micelles in respiratory epithelial cells[J].Eur J Pharm Biopharm,2017,114:29—37.
[27]Chang C,Wei H,Quan CY,et al.Fabrication of thermosensitive PCL-PNIPAAm-PCL triblock copolymeric micelles for drug delivery[J].J Polym Sci,Part A:Polym Chem,2008,46(9):3048—3057.
[28]Zeng X,Guo L,Ma LF.Preparation and characterization of glycyrrhetinic acid-modifi ed poly(ethylene glycol)-poly(b-benzyl-L-asparate)nanoparticles as liver-targeted delivery[J].Colloid Polym Sci,2015,293(1):319—328.
[29]杨卓理,杨可伟,李馨儒,等.两性霉素B的聚乙二醇-聚乳酸胶束的制备及其体外释放动力学[J].中国药学杂志,2007,42(7):519—523.
[30]Cheng F,Guan X,Cao H,et al.Characteristic of core materials in polymeric micelles effect on their micellar properties studied by experimental and DPD simulation methods[J].Int J Pharm,2015,492(1-2):152—160.
[31]毛世瑞,田野,王琳琳.药物纳米载体——聚合物胶束的研究进展[J].沈阳药科大学学报,2010,27(12):979—986.
[32]李文渊,童丽,热增才旦,等.纳米胶束作为药物载体的研究进展[J].中国执业药师,2009,6(12):36—40.
[33]Kozlov MY,Melik-Nubarov NS,Batrakova EV,et al.Relationship between Pluronic block copolymer structure,critical micellization concentration and partitioning coefficients of low mole cularmasssolutes[J].Macromolecules,2000,33(9):3305—3313.
[34]Lavasanifar A,Samuel J,Kwon GS.Poly(ethylene oxide)-block-poly(L-amino acid)micelles for drug delivery[J].Adv Drug Deliv Rev,2002,54(2):169—190.
[35]李平祝,李馨儒,周鹤翔,等.药物与载体材料相容性的预测方法研究[J].中国新药杂志,2009,18(3):262—266.
[36]Cao J,Lu A,Li C,et al.Effect of architecture on the micellar properties of poly(e-caprolactone)containing sulfobetaines[J].Colloids Surf B Biointerfaces,2013,112:35—41.
[37]He YY,Zhang Y,Gu CH,et al.Micellar carrier based on methoxy poly(ethylene glycol)-block-poly(epsiloncaprolactone)block copolymers bearing ketone groups on the polyester block for doxorubicin delivery[J].J Mater Sci Mater Med,2010,21(2):567—574.
[38]Aliabadi HM,Mahmud A,Sharifabadi AD,et al.Micelles of methoxy poly(ethylene oxide)-b-poly(epsilon-caprolactone)as vehicles for the solubilization and controlled delivery of cyclosporine A[J].J Controlled Release,2005,104(2):301—311.
[39]崔福德.药剂学[M].7版.北京:人民卫生出版社,2013:366—367.
[40]邱立朋,龙苗苗,田晨敏,等.载多柔比星透明质酸聚合物胶束的制备及其抗肿瘤活性[J].中国医药工业杂志,2016,47(3):294—298.
[41]杜向党,连明香,陈玉霞,等.恩诺沙星聚合物胶束的制备及体外释放[J].中国兽医学报,2012,32(3):432—436.
[42]关延彬,左岚,饶子超,等.伊曲康唑Pluronic P123聚合物胶束的制备工艺研究[J].中国药学杂志,2011,46(6):434—439.
[43]Yang L,El Ghzaoui A,Li S.In vitro degradation behavior of poly(lactide)-poly(ethylene glycol)block copolymer micelles in aqueous solution[J].Int J Pharm,2010,400(1-2):96—103.
[44]Liu J,Huang W,Pang Y,et al.Self-assembled micelles from an amphiphilic hyperbranched copolymer with polyphosphate arms for drug delivery[J].Langmuir,2010,26(13):10585—10592.
[45]李远达.5-氟尿嘧啶聚合物胶束的制备及抑制肿瘤活性研究[D].广州:广东药学院硕士学位论文,2011.
[46]金光明,金明姬,尹学哲,等.聚合物纳米载药系统的研究现状[J].中国新药杂志,2016,25(5):548—553.
[47]Zhao YZ,Sun CZ,Lu CT,et al.Characterization and antitumor activity of chemical conjugation of doxorubicin in polymeric micelles(DOX-P)in vitro[J].Cancer Lett,2011,311(2):187—194.
[48]She W,Li N,Luo K,et al.Dendronized heparin-doxorubicin conjugate based nanoparticle as p H-responsive drug delivery system for cancer therapy[J].Biomaterials,2013,34(9):2252—2264.
[49]梁润成.两亲性b-环糊精星型聚合物的合成及其胶束给药体系的研究[D].广州:广东药学院硕士学位论文,2013.
[50]Kataoka K,Matsumoto T,Yokoyama M,et al.Doxorubicinloaded poly(ethylene glycol)-poly(beta-benzyl-L-aspartate)copolymer micelles:their pharmaceutical characteristics and biological signifi cance[J].J Controlled Release,2000,64(1-3):143—153.
[51]Yokoyama M,Fukushima S,Uehara R,et al.Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor[J].J Controlled Release,1998,50(1-3):79—92.
[52]张跃庭,董岸杰,邓联东,等.水溶性紫杉醇两亲性共聚物纳米胶束研究[J].化学工程,2005,33(2):39—43.
[53]Rahim NA,Audouin F,Twamley B,et al.Synthesis of poly(4-vinyl pyridine-b-methyl methacrylate)by MAMASG1 initiated sequential polymerization and formation of metal loaded block copolymer inverse micelles[J].Eur Polym J,2012,48(5):990—996.
[54]余巧,潘仕荣,杜卓.紫杉醇自组装核壳型纳米胶束的制备与性能[J].药学学报,2008,43(4):408—414.
[55]Yu BG,Okano T,Kataoka K,et al.Polymeric micelles for drug delivery:solubilization and haemolytic activity of amphotericin B[J].J Controlled Release,1998,53(1-3):131—136.
[2]Huang R,Xiang L,Liu Y,et al.Synthesis and in vitro evaluation of p H-sensitive PEG-I-d C16 block polymer micelles foranticancer drug delivery[J].JPharm Pharmacol,2016,68(6):751—761.
[3]Sun T,Li P,Oh JK.Dual location dual reduction/photoresponsive block copolymer micelles:disassembly and synergistic release[J].Macromol Rapid Commun,2015,36(19):1742—1748.
[4]Wang M,Hu H,Sun Y,et al.A pH-sensitive gene delivery system based on folic acid-PEG-chitosan-PAMAM-plasmid DNA complexes for cancer cell targeting[J].Biomaterials,2013,34(38):10120—10132.
[5]郑毅.抗人CD40单克隆抗体免疫纳米载药胶束的制备及其生物学特性的研究[D].苏州:苏州大学硕士学位论文,2013.
[6]Yu J,Li Z,Wang W,et al.Anticancer 20(R)-dammarane-3b,12b,20,25-tetrol-loaded polymeric micelles:Preparation,quantification and pharmacokinetics[J].J Chromatogr B Analyt Technol Biomed Life Sci,2016,1022:13—20.
[7]Perrut M,Jung J,Leboeuf F.Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fl uid processes.Part I:Micronization of neat particles[J].Int J Pharm,2005,288(1):3—10.
[8]Xiong XB,UludaeH,Lavasanifar A.Virus-mimetic polymeric micelles for targeted si RNA delivery[J].Biomaterials,2010,31(22):5886—5893.
[9]Li X,Li P,Zhang Y,et al.Novel mixed polymeric micelles for enhancing delivery of anticancer drug and overcoming multidrug resistance in tumor cell lines simultaneously[J].Pharm Res,2010,27(8):1498—1511.
[10]He Z,Wan X,Schulz A,et al.A high capacity polymeric micelle of paclitaxel:Implication of high dose drug therapy to safety and in vivo anti-cancer activity[J].Biomaterials,2016,101:296—309.
[11]Isoda K,Kanayama N,Fujita M,et al.DNA terminal mismatch-induced stabilization of polymer micelles from RAFT-generated poly(N-isopropylacrylamide)-DNA block copolymers[J].Chem Asian J,2013,8(12):3079—3084.
[12]Zhou W,Li C,Wang Z,et al.Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement[J].J Nanopart Res,2016,18(9):275.
[13]王狄狮,周艳霞,李承洧,等.p H敏感聚合物胶束给药系统的研究进展[J].中国新药杂志,2016,25(19):2218—2224.
[14]Gothwal A,Khan I,Gupta U.Polymeric micelles:recent advancements in the delivery of anticancer drugs[J].Pharm Res,2016,33(1):18—39.
[15]Le Garrec D,Gori S,Luo L,et al.Poly(N-vinylpyrrolidone)-block-poly(D,L-lactide)as a new polymeric solubilizer for hydrophobic anticancer drugs:in vitro and in vivo evaluation[J].J Control Release,2004,99(1):83—101.
[16]Wu WC,Chang HH.Fluorescent polymeric micelles containing fluorenederivatives formonitoring drug encapsulation and release[J].Colloid Polym Sci,2015,293(2):453—462.
[17]Li J,Li Z,Li M,et al.Synergistic effect and drug-resistance relief of paclitaxel and cisplatin caused by co-delivery using polymeric micelles[J].J Appl Polym Sci,2015,132(6):41440—41448.
[18]Wang Y,Zhu DD,Zhou J,et al.Mesoscopic simulation studies on the formation mechanis mof drugloaded polymeric micelles[J].Colloids Surf B:Biointerfaces,2015,136:536—544.
[19]Shi J,Zhang J,Shen Y,et al.Arginine-stabilized m PEGP DLLA(50/50)polymericmicelles of docetaxel by electrostatic mechanism for tumor-targeted delivery[J].Drug Deliv,2015,22(2):168—181.
[20]Vekariya RL,Ray D,Aswal VK,et al.Effect of ionic liquids on microstructures of micellar aggregates formed by PEOPPO-PEO block copolymer in aqueous solution[J].Colloids Surf A Physicochem Eng Asp,2014,462:153—161.
[21]Ali R,Farah A,Binkhathlan Z.Development and characterization of methoxy poly(ethylene oxide)-blockpoly(e-caprolactone)(PEO-b-PCL)micelles as vehicles for the solubilization and delivery of tacrolimus[J].Saudi Pharm J,2017,25(2):258—265.
[22]Gao Y,Li Y,Li Y,et al.PSMA-mediated endosome escapeaccelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular traffi cking[J].Nanoscale,2015,7(2):597—612.
[23]Li J,Zhou Y,Li C,et al.Poly(2-ethyl-2-oxazoline)-doxorubicin conjugate-based dual endosomal p H-sensitive micelles with enhanced antitumor efficacy[J].Bioconjug Chem,2015,26(1):110—119.
[24]Jiang C,Wang H,Zhang X,et al.Deoxycholic acid-modifi ed chitooligosaccharide/m PEG-PDLLA mixed micelles loaded with paclitaxel for enhanced antitumor efficacy[J].Int J Pharm,2014,475(1-2):60—68.
[25]Singh RP,Sharma G,Sonali,et al.Transferrin receptor targeted PLA-TPGS micelles improved effi cacy and safety in docetaxel delivery[J].Int J Biol Macromol,2016,83:335—344.
[26]Hu X,Yang FF,Liu CY,et al.In vitro uptake and transport studies of PEG-PLGA polymeric micelles in respiratory epithelial cells[J].Eur J Pharm Biopharm,2017,114:29—37.
[27]Chang C,Wei H,Quan CY,et al.Fabrication of thermosensitive PCL-PNIPAAm-PCL triblock copolymeric micelles for drug delivery[J].J Polym Sci,Part A:Polym Chem,2008,46(9):3048—3057.
[28]Zeng X,Guo L,Ma LF.Preparation and characterization of glycyrrhetinic acid-modifi ed poly(ethylene glycol)-poly(b-benzyl-L-asparate)nanoparticles as liver-targeted delivery[J].Colloid Polym Sci,2015,293(1):319—328.
[29]杨卓理,杨可伟,李馨儒,等.两性霉素B的聚乙二醇-聚乳酸胶束的制备及其体外释放动力学[J].中国药学杂志,2007,42(7):519—523.
[30]Cheng F,Guan X,Cao H,et al.Characteristic of core materials in polymeric micelles effect on their micellar properties studied by experimental and DPD simulation methods[J].Int J Pharm,2015,492(1-2):152—160.
[31]毛世瑞,田野,王琳琳.药物纳米载体——聚合物胶束的研究进展[J].沈阳药科大学学报,2010,27(12):979—986.
[32]李文渊,童丽,热增才旦,等.纳米胶束作为药物载体的研究进展[J].中国执业药师,2009,6(12):36—40.
[33]Kozlov MY,Melik-Nubarov NS,Batrakova EV,et al.Relationship between Pluronic block copolymer structure,critical micellization concentration and partitioning coefficients of low mole cularmasssolutes[J].Macromolecules,2000,33(9):3305—3313.
[34]Lavasanifar A,Samuel J,Kwon GS.Poly(ethylene oxide)-block-poly(L-amino acid)micelles for drug delivery[J].Adv Drug Deliv Rev,2002,54(2):169—190.
[35]李平祝,李馨儒,周鹤翔,等.药物与载体材料相容性的预测方法研究[J].中国新药杂志,2009,18(3):262—266.
[36]Cao J,Lu A,Li C,et al.Effect of architecture on the micellar properties of poly(e-caprolactone)containing sulfobetaines[J].Colloids Surf B Biointerfaces,2013,112:35—41.
[37]He YY,Zhang Y,Gu CH,et al.Micellar carrier based on methoxy poly(ethylene glycol)-block-poly(epsiloncaprolactone)block copolymers bearing ketone groups on the polyester block for doxorubicin delivery[J].J Mater Sci Mater Med,2010,21(2):567—574.
[38]Aliabadi HM,Mahmud A,Sharifabadi AD,et al.Micelles of methoxy poly(ethylene oxide)-b-poly(epsilon-caprolactone)as vehicles for the solubilization and controlled delivery of cyclosporine A[J].J Controlled Release,2005,104(2):301—311.
[39]崔福德.药剂学[M].7版.北京:人民卫生出版社,2013:366—367.
[40]邱立朋,龙苗苗,田晨敏,等.载多柔比星透明质酸聚合物胶束的制备及其抗肿瘤活性[J].中国医药工业杂志,2016,47(3):294—298.
[41]杜向党,连明香,陈玉霞,等.恩诺沙星聚合物胶束的制备及体外释放[J].中国兽医学报,2012,32(3):432—436.
[42]关延彬,左岚,饶子超,等.伊曲康唑Pluronic P123聚合物胶束的制备工艺研究[J].中国药学杂志,2011,46(6):434—439.
[43]Yang L,El Ghzaoui A,Li S.In vitro degradation behavior of poly(lactide)-poly(ethylene glycol)block copolymer micelles in aqueous solution[J].Int J Pharm,2010,400(1-2):96—103.
[44]Liu J,Huang W,Pang Y,et al.Self-assembled micelles from an amphiphilic hyperbranched copolymer with polyphosphate arms for drug delivery[J].Langmuir,2010,26(13):10585—10592.
[45]李远达.5-氟尿嘧啶聚合物胶束的制备及抑制肿瘤活性研究[D].广州:广东药学院硕士学位论文,2011.
[46]金光明,金明姬,尹学哲,等.聚合物纳米载药系统的研究现状[J].中国新药杂志,2016,25(5):548—553.
[47]Zhao YZ,Sun CZ,Lu CT,et al.Characterization and antitumor activity of chemical conjugation of doxorubicin in polymeric micelles(DOX-P)in vitro[J].Cancer Lett,2011,311(2):187—194.
[48]She W,Li N,Luo K,et al.Dendronized heparin-doxorubicin conjugate based nanoparticle as p H-responsive drug delivery system for cancer therapy[J].Biomaterials,2013,34(9):2252—2264.
[49]梁润成.两亲性b-环糊精星型聚合物的合成及其胶束给药体系的研究[D].广州:广东药学院硕士学位论文,2013.
[50]Kataoka K,Matsumoto T,Yokoyama M,et al.Doxorubicinloaded poly(ethylene glycol)-poly(beta-benzyl-L-aspartate)copolymer micelles:their pharmaceutical characteristics and biological signifi cance[J].J Controlled Release,2000,64(1-3):143—153.
[51]Yokoyama M,Fukushima S,Uehara R,et al.Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor[J].J Controlled Release,1998,50(1-3):79—92.
[52]张跃庭,董岸杰,邓联东,等.水溶性紫杉醇两亲性共聚物纳米胶束研究[J].化学工程,2005,33(2):39—43.
[53]Rahim NA,Audouin F,Twamley B,et al.Synthesis of poly(4-vinyl pyridine-b-methyl methacrylate)by MAMASG1 initiated sequential polymerization and formation of metal loaded block copolymer inverse micelles[J].Eur Polym J,2012,48(5):990—996.
[54]余巧,潘仕荣,杜卓.紫杉醇自组装核壳型纳米胶束的制备与性能[J].药学学报,2008,43(4):408—414.
[55]Yu BG,Okano T,Kataoka K,et al.Polymeric micelles for drug delivery:solubilization and haemolytic activity of amphotericin B[J].J Controlled Release,1998,53(1-3):131—136.