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

Preparation and in vitro Release Kinetics of Amphotericin B-Loaded Poly (Ethyleneglycol)-Poly (dl-Lactide) Block Copolymer Micelles

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。

OBJECTIVE To prepare AraB-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 scat- tering. The critical association concentration （CAC） was detected with fluorescence method using pyrene as a probe. The in vitro release of the AraB-loaded PEG-PLA micelles was evaluated using a dialysis method. RESULTS Pictures by transmission electron microscopy revealed spherical and core-shell AraB-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 AraB 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.