摘要
目的制备两性霉素B的聚乙二醇-聚乳酸嵌段共聚物胶束,对其物理化学性质和体外释药特性进行评价。方法采用阴离子聚合法合成了一系列聚乙二醇-聚乳酸嵌段共聚物;用透析法制备了聚合物胶束;用透射电镜观察了聚合物胶束的形态;用激光散射法测定了聚合物胶束的粒径及其分布;采取荧光探针法测定了聚合物的临界缔合浓度;用透析法考察了载药聚合物胶束的体外释放动力学。结果聚合物胶束大小均匀,具有球形核-壳结构,平均粒径范围为28～49nm,并随着疏水链段的增长,胶束粒径逐渐增大;3种聚合物的临界缔合浓度均较低,分别为1.87×10-7,1.45×10-7,9.61×10-8mol·L-1;两性霉素B聚合物胶束的体外释放缓慢,符合一级动力学特征。结论聚乙二醇-聚乳酸嵌段共聚物胶束可作为疏水性药物的纳米级长循环载体,具有很好的应用前景。
Abstract
OBJECTIVE To prepare AmB-loaded poly(ethylene glycol)-poly(dl-lactide)(PEG-PLA)block copolymer micelles and evaluate their physicochemical properties and drug release properties in vitro.METHODS The PEG-PLA block copolymers were synthesized using anionic polymerazation method.Polymer micelles were prepared by dialysis procedure and their morphology was observed by the transmission electron microscopy(TEM).The mean size and size distribution of the micelles were determined by dynamic light scattering.The critical association concentration(CAC)was detected with fluorescence method using pyrene as a probe.The in vitro release of the AmB-loaded PEG-PLA micelles was evaluated using a dialysis method.RESULTS Pictures by transmission electron microscopy revealed spherical and core-shell AmB-loaded PEG-PLA micelles.The mean diameter range of the three kinds of polymeric micelles was from 28 to 49 nm,and an increase in the micellar size was observed with the length of hydrophobic blocks.The CACs of the polymeric micelles were 1.87×10-7,1.45×10-7,9.61×10-8 mol·L-1,respectively.The sustained release in vitro of AmB from PEG-PLA micelles was evidenced.The in vitro release behavior were described by the first order equation.CONCLUSION The poly(ethylene glycol)-poly(dl-lactide)block copolymer micelles may serve as nanoscopic,long-circulating carriers for hydrophobic drugs.
关键词
嵌段共聚物 /
聚合物胶束 /
两性霉素B
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Key words
block copolymers /
polymeric micelle /
amphotericin B /
in vitro release
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杨卓理;杨可伟;李馨儒;刘艳.
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(07): 519-523
YNG Zhuo-li;YNG Ke-wei;LI Xin-ru;LIU Yn.
Preparation and in vitro Release Kinetics of Amphotericin B-Loaded Poly (Ethyleneglycol)-Poly (dl-Lactide) Block Copolymer Micelles [J]. Chinese Pharmaceutical Journal, 2007, 42(07): 519-523
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参考文献
[1］KATAOKA K，HARADA A，NAGASAKI Y. Block copolymer micelles for drug delivery： design，characterization and biological significance[J］.Adv Drug Deliv Rev，2001，47：113-131.
[2］ALLEN C，MAYSINGER D，EISENBERG A. Nano-engineering block copolymer aggregates for drug delivery[J］. Colloids Surf B Biointerfaces，1999，16： 3-27.
[3］TORCHILIN V P. Structure and design of polymeric surfactant-based drug delivery systems [J］. J Controlled Release，2001，73 ：137-172.
[4］TORCHILIN V P. PEG-based micelles as carriers of contrast agents for different imaging modalities[J］.Adv Drug Deliv Rev，2002，54：235-252.
[5］CHEN X Q，JIN Y Y.New Edition of Pharmacology（新编药物学）[M］.Vol 14.Beijing：People′s Medical Publishing House，1997，107.
[6］KWON G，NAITO M，YOKOYAMA M，et al. Micelles based on AB block copolymers of poly(ethylene oxide) and poly(β-benzyl L-aspartate) [J］.Langmuir，1993，9： 945-949.
[7］WILHELM M，ZHAO C L， WANG Y C，et al.Poly(styrene-ethylene oxide) block copolymer micelle formation in water： A fluorescence probe study[J］.Macromolecules，1991，24：1033-1040.
[8］LUKYANOV A N，VLADIMIR P. Torchilin micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs[J］.Adv Drug Deliv Revi，2004，56：1273-1289.
[9］YU B G，OKANO T，KATAOK K，et al.Polymeric micelles for drug delivery： solubilization and haemolytic activity of amphotericin B[J］. J Controlled Release ，1998，53：131-136.
[10］STOODLEY R A，SHEPHERD J A，WASAN B，et al.Amphotericin B interactions with a DOPC monolayer. Electrochemical investigations[J］. Biochim Biophys Acta，2002，1564：289-297.
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脚注
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