Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Eur J Pharm Sci. 2012 Aug 30;47(1):179-89. doi: 10.1016/j.ejps.2012.05.015. Epub 2012 Jun 7.
In order to enhance paclitaxel oral bioavailability, mixed polymeric micelles that comprised of pluronic copolymers and low molecular weight heparin-all-trans-retinoid acid (LHR) conjugate were developed. PTX-loaded mixed polymeric micelles (MPMs) were prepared by dialysis method with high drug loading 26.92 ± 2.08% and 25.82 ± 1.9% for F127/LHR and P188/LHR MPMs respectively, and were found to be spherical in shape with an average size of around 140 nm and a narrow size distribution. In vitro release study showed that pluronic/LHR MPMs exhibited delayed release characteristics compared to Taxol and faster drug release profile compared to LHR plain polymeric micelles (PPMs). The cytotoxic activity of PTX-loaded pluronic/LHR MPMs was slightly higher than LHR PPMs in MCF-7 cells (p<0.01). In situ effective permeability of PTX through rat small intestine was 5- to 6-fold higher with mixed micelles than that of Taxol. Moreover, pluronic/LHR MPMs achieved significantly higher AUC and C(max) level than both of LHR PPMs and Taxol. This enhancement might be due to the inhibition of both P-glycoprotein efflux system and cytochrome P450 metabolism by pluronic copolymers. The current results encourage further development of paclitaxel mixed polymeric micelles as an oral drug delivery system.
为了提高紫杉醇的口服生物利用度，开发了由两亲性嵌段共聚物 Pluronic 和低分子量肝素全反式维甲酸（LHR）偶联物组成的混合聚合物胶束。采用透析法制备载紫杉醇的混合聚合物胶束（MPMs），载药量分别为 26.92±2.08%和 25.82±1.9%，对于 F127/LHR 和 P188/LHR MPMs 而言，其形态均为球形，平均粒径约为 140nm，粒径分布较窄。体外释放研究表明，与 Taxol 相比，Pluronic/LHR MPMs 表现出延迟释放的特点，与 LHR 普通聚合物胶束（PPMs）相比，释放速度更快。载紫杉醇的 Pluronic/LHR MPMs 在 MCF-7 细胞中的细胞毒性活性略高于 LHR PPMs（p<0.01）。与 Taxol 相比，载药混合胶束通过大鼠小肠的有效渗透系数提高了 5-6 倍。此外，Pluronic/LHR MPMs 的 AUC 和 C(max)水平均显著高于 LHR PPMs 和 Taxol。这种增强可能是由于 Pluronic 嵌段共聚物抑制了 P-糖蛋白外排系统和细胞色素 P450 代谢。目前的结果鼓励进一步开发紫杉醇混合聚合物胶束作为口服药物递送系统。
