Ge Yanxiu, Zhao Yanli, Li Lingbing
a Department of Pharmaceutics , School of Pharmacy, Shandong University , Jinan , Shandong Province , China.
Drug Deliv. 2016 Sep;23(7):2555-2565. doi: 10.3109/10717544.2015.1028604. Epub 2015 Apr 8.
In present study, two types of micelles based on sodium cholate (NaC) were prepared through non-covalent bonding interaction and the potential of micelles as oral drug delivery systems for paclitaxel (PTX) was evaluated. Pluronic-chitosan (F127-CS) and Pluronic-poly (acrylic acid) (F127-PAA) copolymers were synthesized. Electrostatic interaction and hydrogen bond were used to prepare F127-CS/NaC micelles and F127-PAA/NaC micelles, respectively. The physicochemical characteristics of micelles were determined. An average diameter of 67.5 nm and unimodal pattern of size distribution were observed for F127-CS/NaC micelles. While for F127-PAA/NaC micelles, an average diameter of 85.89 nm and non-unimodal pattern of size distribution were observed. The results revealed that F127-CS/NaC micelles were more integrated than F127-PAA/NaC micelles. Further experiments showed that the F127-CS/NaC micelles had a higher drug-loading content of 12.8% and a lower critical micelle concentration (CMC) of 2.5 × 10mol/L compared with F127-PAA/NaC micelles. In vitro cytotoxicity analysis demonstrated that the PTX-loaded F127-CS/NaC micelles were of great efficiency in inhibiting the growth of drug-resistant breast cancer MCF-7 cells (MCF-7/Adr). The intragastric administration of the PTX-loaded F127-CS/NaC micelles in rats provided a 4.33-fold higher absolute bioavailability compared to commercial Taxol®, indicating an efficient oral absorption of PTX delivered by micelles. These findings signify that F127-CS/NaC micelle may be a promising carrier for the delivery of PTX.
在本研究中，通过非共价键相互作用制备了两种基于胆酸钠（NaC）的胶束，并评估了胶束作为紫杉醇（PTX）口服给药系统的潜力。合成了泊洛沙姆-壳聚糖（F127-CS）和泊洛沙姆-聚丙烯酸（F127-PAA）共聚物。分别利用静电相互作用和氢键制备了F127-CS/NaC胶束和F127-PAA/NaC胶束。测定了胶束的物理化学特性。观察到F127-CS/NaC胶束的平均直径为67.5nm，粒径分布呈单峰模式。而对于F127-PAA/NaC胶束，观察到平均直径为85.89nm，粒径分布呈非单峰模式。结果表明，F127-CS/NaC胶束比F127-PAA/NaC胶束更完整。进一步实验表明，与F127-PAA/NaC胶束相比，F127-CS/NaC胶束具有更高的载药量，为12.8%，更低的临界胶束浓度（CMC），为2.5×10mol/L。体外细胞毒性分析表明，负载PTX的F127-CS/NaC胶束在抑制耐药性乳腺癌MCF-7细胞（MCF-7/Adr）生长方面具有很高的效率。在大鼠体内胃内给药负载PTX的F127-CS/NaC胶束，与市售的泰素相比，绝对生物利用度提高了4.33倍，表明胶束递送的PTX具有高效的口服吸收。这些发现表明，F127-CS/NaC胶束可能是一种有前途的PTX递送载体。
