壳聚糖季铵盐表面修饰对载紫杉醇PLGA微球体外药效学的影响

Pharmacology Efficacy in vitro of PTX-PLGA Microspheres and Surface Modified PTX-PLGA Microspheres by Quaternized Chitosan

采用聚(乳酸羟基乙酸)共聚物(PLGA)纳微球装载紫杉醇,并用壳聚糖季铵盐(HTCC)对PLGA微球表面进行镀层修饰,比较了修饰前后载药微球的形貌、粒径、电位、载药率、释药行为和细胞杀伤效果.结果表明,修饰后微球表面圆整光滑,平均粒径为882nm,载药率可达5.15%,包埋率达70.46%,体外释药22d累积释药率为70.17%,与修饰前没有显著性差异;但修饰后微球表面电荷由修饰前的14.8mV翻转为+36.7mV,肿瘤细胞对PLGA和HTCC-PLGA载药微球的内吞量分别是Taxol的5.6和9.7倍,且HTCC-PLGA载药微球对细胞杀伤效果显著,是一种有潜力的难溶性药物递送系统.

Poly（dl-lactic-co-glycolic acid） （PLGA） microspheres containing PTX and surface modified PTX-PLGA microspheres with HTCC were prepared by premix membrane emulsification combined with solvent evaporation. Then the corresponding effects on surface morphology, loading and encapsulation efficiencies, release profile and antitumor activity in vitro were systematically investigated. The results showed that the mean diameter of PTX-loaded HTCC-PLGA microspheres was 882 nm, the loading and encapsulation efficiencies were 5.15% and 70.46%, and the cumulative release rate in vitro for 22 d was 70.17%, which had little difference from PTX-loaded PLGA microspheres. However, PTX-loaded HTCC-PLGA microspheres showed positive surface charge as ＋36.7 mV and PLGA was -14.8 mV. The intracellular PTX incubated with PTX-loaded PLGA and PLGA-HTCC microspheres was 5.6 and 9.7 times as much as that of Taxol~, and HTCC-PLGA microspheres showed lower cell viability than PLGA microspheres. Therefore, PTX-loaded HTCC-PLGA microspheres were the potential delivery system for insoluble drug PTX.