Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia.
Biomed Pharmacother. 2018 Oct;106:1461-1468. doi: 10.1016/j.biopha.2018.07.102. Epub 2018 Jul 24.
In the present study, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanoparticles were successfully prepared and coated with chitosan (CS). The prepared nanoparticles (NPs) were evaluated for their particle size, zeta potential, particle morphology, drug entrapment efficiency (EE%), and in vitro drug release profile. The anticancer activity of DTX-loaded NPs was assessed in human HT29 colon cancer cell line utilizing MTT assay. The pharmacokinetics of DTX-loaded NPs was monitored in Wistar rats in comparison to DTX solution. The prepared NPs exhibited particle sizes in the range 177.1 ± 8.2-287.6 ± 14.3 nm. CS decorated NPs exhibited a significant increase in particle size and a switch of zeta potential from negative to positive. In addition, high EE% values were obtained for CS coated PCL NPs and PLGA NPs as 67.1 and 76.2%, respectively. Moreover, lowering the rate of DTX in vitro release was achieved within 48 h by using CS coated NPs. Furthermore, a tremendous increase in DTX cytotoxicity was observed by CS-decorated PLGA NPs compared to all other NPs including DTX-free-NPs and pure DTX. The in vivo study revealed significant enhancement in DTX bioavailability from CS-decorated PLGA NPs with more than 4-fold increase in AUC compared to DTX solution. In conclusion, CS-decorated PLGA NPs are a considerable DTX-delivery carrier with magnificent antitumor efficacy.
在本研究中，成功制备了载多西紫杉醇（DTX）的聚乳酸-共-羟基乙酸（PLGA）和聚己内酯（PCL）纳米粒，并对其进行了壳聚糖（CS）包覆。对所制备的纳米粒（NPs）的粒径、Zeta 电位、颗粒形态、药物包封效率（EE%）和体外药物释放特性进行了评价。采用 MTT 法评估了载 DTX NPs 在人 HT29 结肠癌细胞系中的抗癌活性。并与 DTX 溶液相比，监测了载 DTX NPs 在 Wistar 大鼠体内的药代动力学。所制备的 NPs 的粒径在 177.1±8.2-287.6±14.3nm 范围内。CS 修饰的 NPs 的粒径显著增加，Zeta 电位从负变为正。此外，CS 涂覆的 PCL NPs 和 PLGA NPs 分别获得了高达 67.1%和 76.2%的高 EE%值。此外，通过使用 CS 涂覆的 NPs，可在 48h 内显著降低 DTX 的体外释放率。此外，与所有其他 NPs（包括无 DTX-NPs 和纯 DTX）相比，CS 修饰的 PLGA NPs 显著提高了 DTX 的细胞毒性。体内研究表明，与 DTX 溶液相比，CS 修饰的 PLGA NPs 显著提高了 DTX 的生物利用度，AUC 增加了 4 倍以上。总之，CS 修饰的 PLGA NPs 是一种有前途的 DTX 递送载体，具有优异的抗肿瘤疗效。
