pH敏感聚(2-乙基-2-噁唑啉)-壳聚糖-阿霉素共聚物胶束的制备及性质考察

Preparation and characteristics of poly (2-ethyl-2-oxazoline)-chitosan-doxorubicin polymeric micelles

目的合成pH敏感两亲性接枝共聚物聚(2-乙基-2-噁唑啉)-壳聚糖-阿霉素(PEOz-g-CS-HyzDOX),采用透析法制备阿霉素pH敏感两亲性共聚物胶束并对其相关的制剂学性质、细胞抑制及细胞摄取行为进行考察。方法分别利用透射电镜(TEM)、动态光散射法(DLS)和zeta电位分析仪对胶束的形态、粒径和表面电位进行表征;采用透析法考察载药聚合物胶束的体外释放行为;采用MTT法考察聚合物胶束的细胞抑制作用。结果反应产物使用红外及核磁表征,确定为目标产物;PEOz-g-CS-Hyz-DOX聚合物胶束载药量为4.2%。采用透析法制备的载阿霉素聚(2-乙基-2-噁唑啉)-壳聚糖丁二酸单甲酯胶束(PEOz-g-CSMS/DOX)载药量可达5.62%,包封率为59.35%;两种胶束的粒径均较小且粒径分布很窄,胶束粒子为类球形且分散良好;两种胶束释药行为体现pH敏感性;PEOz-g-CS-Hyz-DOX聚合物胶束体外细胞毒作用及细胞摄取均优于PEOz-g-CSMS/DOX胶束和阿霉素溶液。结论以壳聚糖为载体的化学腙键释药胶束作为抗肿瘤药物的药物传递系统具有可行性及良好的应用前景。

Objective To synthesize poly （2-ethyl-2-oxazoline）-chitosan-doxorubicin （PEOz-g-CS-Hyz- DOX） and study the characteristics, the inhibition effects and cellular uptake of the pH sensitive amphiphilic copolymer miceUes. Methods The morphology, diameter and surface potential of the micelles were character- ized by transmission electron microscopy （TEM）, dynamic light scattering （DLS）and zeta potential analy- zer, respectively. The in vitro release behavior of DOX from polymeric micelles was investigated using dialy- sis method. The cellular uptake of polymeric micelles were inveatigated. Results The synthesized polymers were characterized by PT-IR, 1H-NMR. The results indicated that drug-loaded amount and entrapment effi- ciency of the PEOz-g-CSMS/DOX micelles was 5.62% and 59.35 %, respectively. The drug-loaded amount and grafting rate of PEOz-g-CS-Hyz-DOX were 4% and 61.5%, respectively. The micelle was globular- shaped and had small diameter with a narrow size distribution. The pH-sensitive drug release behavior of the micelles was pH dependent. The cytotoxic against MCF-7 cells in vitro and cellular uptake of PEOz-g-CS- Hyz-DOX were stronger than the PEOz-g-CSMS/DOX micelles and DOX solution. Conclusions It can be concluded that the copolymer micelles using chitosan carder by chemical acylhydrazone releasing drug may be applied as promising drug delivery system for anti-tumor drugs.