pH敏感释药两亲性壳聚糖共聚物胶束的制备及其性质考察

目的在合成了两亲性接枝共聚物丁酰基-羧甲基-壳聚糖(butyryl-carboxymethyl-chitosan,BR-CM-CS)的基础上,采用化学键合载药方式结合透析法制备了阿霉素pH敏感两亲性共聚物胶束并对其相关性质进行考察。方法利用芘荧光探针技术测定胶束的临界胶束浓度(CMC);通过透析法结合紫外分光光度法测定胶束的载药量及包封率;分别利用透射电镜(TEM)、扫描电镜(SEM)、动态光散射法(DLS)和zeta电位分析仪对胶束及其冷冻干燥产品的形态、粒径和表面电位进行了表征;采用透析法考察了载药聚合物胶束的体外释放行为。结果胶束的CMC值为1.0 mg.L-1,载药量可达12.5%,包封率为89.1%;胶束的粒度分布很窄,平均粒径为205.2 nm;胶束粒子为类球形且分散良好,其表面zeta电位值为25.94 mV;胶束释药行为体现pH敏感性。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传递系统具有可行性及良好的应用前景。

Preparation and characteristics of amphiphilic chitosan polymeric micelle by pH-sensitive chemical bond

Objective To present the preparation of chemical-bond doxorubicin-loaded pH-sensitive amphiphilic copolymer micelles using dialysis method based on the synthesis of amphiphilic graft copolymer butyryl-carboxymethyl-chitosan(BR-CM-CS).Methods The critical micelle concentration(CMC)was measured by pyrene fluorescent probe technique.The entrapment efficiency and drug-loaded amount were determined by UV and dialysis.The morphology,diameter and surface potential of the micelles were characterized by transmission electron microscopy(TEM),scan electron microscopy(SEM),dynamic light scattering(DLS)and zeta potential analyzer,respectively.The in vitro release behavior of DOX from polymeric micelles was investigated using dialysis method.Results The results indicated that the CMC,drug-loaded amount and entrapment efficiency of the micelles were 1.0 mg·L-1,12.5% and 89.1%,respectively.The micelles had a narrow size distribution,with a mean diameter of 205 nm.The micelle was globular-shaped and its zeta potential was 25.94 mV.In PBS at pH 7.4,DOX was released in a sustained manner from the micelles;while in PBS at pH 5.0 and 6.8,drug was released more rapidly,which suggested the pH-sensitive drug release behavior of the DOX-hydrazone-BR-CM-CS micelles.Conclusions It can be concluded that the copolymer micelles using chitosan carrier by chemical acylhydrazone releasing drug may be applied as promising drug delivery system for anti-tumor drugs.