半胱氨酸修饰的荷载紫杉醇聚离子复合物胶束口服给药的体内体外研究

In Vitro and in Vivo Evaluation of Cysteine Modified Polyion Complex Micellae for Oral

本文合成了普朗尼克F127-壳聚糖(F127-CS)和普朗尼克F127-半胱氨酸(F127-CT)共聚物,采用薄膜分散法以F127-CS、F127-CT和胆酸钠(Na C)为材料构建了聚离子复合物胶束,并以该复合物胶束作为药物载体运载紫杉醇进行口服给药。通过物理化学性质研究,包括粒径分布、Zeta电位、外观形态和临界胶束浓度,进一步证实形成了纳米级球形结构的胶束,并对胶束的体外释放及体内药动力学进行考察。与普朗尼克胶束的载药量(3.35%)相比,F127-CS/F127-CT/Na C胶束载药量提高到12.77%。通过临界胶束浓度的测定证实:在水溶液中F127-CS/F127-CT/Na C胶束比Na C胶束更稳定。药物动力学实验结果显示F127-CS/F127-CT/Na C紫杉醇载药胶束的药-时曲线下的面积是紫杉醇溶液的4倍。因此,F127-CS/F127-CT/Na C胶束是一种理想的紫杉醇口服给药系统。

Pluronic F127-chitosin( F127-CS) and Pluronic F127-cysteine( F127-CT) copolymers were prepared and polyion complex micellae consisting of F127-CS,F127-CT and sodium cholate were constructed by film dispersion method using as an oral drug delivery system for paclitaxel. The physicochemical properties of F127-CS / F127-CT / Na C micellae were systematically studied including size distribution,zeta-potential and morphology to confirm the formation of nanoscale micelle structure with spherical shape. In vitro release behavior and in vivo pharmacokinetics studies are also evaluated. The results showed that the drug-loading content of F127-CS / F127-CT / Na C micellae had been increased to 12. 77%,compared with that of Pluronic micellae( 3. 35 %). It was shown that the F127-CS / F127-CT / Na C micellae were more stable than those of the Na C micellae in the solution by the critical micelle concentration test. The results of pharmacokinetic study in rats demonstrated that the area under the plasma concentration-time curve of paclitaxel-loading F127-CS / F127-CT / Na C micellae was four times greater than that of paclitaxel solution. Therefore,F127-CS /F127-CT / Na C micelles were favourable for oral delivery of paclitaxel.