College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Biomaterials. 2010 Mar;31(8):2371-9. doi: 10.1016/j.biomaterials.2009.11.102. Epub 2010 Jan 19.
A mixed micelle that comprised of MPEG-PLA (MPP) and Pluronic copolymers was developed for enhanced bioavailability and to overcome multidrug resistance of docetaxel in cancer therapy. The mixed micelles that sufficiently solubilized docetaxel were evaluated for the effect of Pluronic copolymers weight ratio on the mixed micelles with respect to drug loading and drug release. In vitro, cell viability and cytotoxicity studies in KB and KBv cells revealed that the mixed micellar formulations were more potent than the commercial docetaxel formulation (Taxotere). In vivo pharmacokinetics study in rats showed that the mixed micelles significantly enhanced the bioavailability of docetaxel (3.6 fold) than Taxotere. Moreover, antitumor activity assessed in KBv cancer xenograft BALB/C nude mice models showed that the mixed micelles significantly reduced the tumor size than the control (Taxotere). Clear differences in the intracellular uptake of docetaxel between MPP and mixed micelles were observed using confocal laser scanning microscopy. This study presents not only a new micelle structure for a diblock-triblock copolymer system, but also a method for enhanced bioavailability of docetaxel and to overcome some of the limitations on its multidrug resistance in cancer therapy.
一种由 MPEG-PLA（MPP）和泊洛沙姆共聚物组成的混合胶束被开发用于提高生物利用度，并克服癌症治疗中多西紫杉醇的多药耐药性。充分溶解多西紫杉醇的混合胶束用于评估泊洛沙姆共聚物的重量比对混合胶束的载药量和药物释放的影响。在体外，KB 和 KBv 细胞的细胞活力和细胞毒性研究表明，与商业多西紫杉醇制剂（泰素帝）相比，混合胶束制剂具有更强的效力。在大鼠体内药代动力学研究中，混合胶束显著提高了多西紫杉醇的生物利用度（3.6 倍）。此外，在 KBv 癌症异种移植 BALB/C 裸鼠模型中的抗肿瘤活性研究表明，与对照组（泰素帝）相比，混合胶束显著减小了肿瘤体积。使用共聚焦激光扫描显微镜观察到多西紫杉醇在 MPP 和混合胶束之间的细胞内摄取存在明显差异。这项研究不仅提出了一种二嵌段-三嵌段共聚物系统的新胶束结构，还提出了一种提高多西紫杉醇生物利用度并克服其在癌症治疗中多药耐药性的一些局限性的方法。
