Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, Pakistan.
Faculty of Pharmacy, University of Lahore, Lahore, Pakistan.
AAPS PharmSciTech. 2019 Jan 15;20(2):81. doi: 10.1208/s12249-019-1297-z.
To achieve remotely directed delivery of anticancer drugs, surface-decorated nanoparticles with ligands are reported. In this study, folic acid- and thiol-decorated chitosan nanoparticles loaded with docetaxel (DTX-NPs) were prepared for enhanced cellular internalization in cancer cells and improved oral absorption. The DTX-NPs were explored through in vitro and in vivo parameters for various parameters. The DTX-NPs were found to be monodisperse nanoparticles with an average particle size of 158.50 ± 0.36 nm, a polydispersity index of 0.36 ± 0.0, a zeta potential of + 18.30 ± 2.52 mV, and an encapsulation efficiency of 71.47 ± 5.62%. The drug release from DTX-NPs followed the Korsmeyer-Peppas model with about 78% of drug release in 12 h. In in vitro cytotoxicity studies against folate receptor, positive MDA-MBB-231 cancerous cells showed improved cytotoxicity with IC of 0.58 μg/mL, which is significantly lower as compared to docetaxel (DTX). Ex vivo permeation enhancement showed an efflux ratio of 0.99 indicating successful transport across the intestine. Oral bioavailability was significantly improved as C and AUC were higher than DTX suspension. Overall, the results suggest that DTX-NPs can be explored as a promising carrier for oral drug delivery.
为实现抗癌药物的远程靶向递送，研究人员报道了表面修饰有配体的纳米粒子。在这项研究中，制备了负载多西紫杉醇（DTX-NPs）的叶酸和巯基修饰壳聚糖纳米粒子，以增强癌细胞内的细胞内化和改善口服吸收。通过体外和体内参数研究了 DTX-NPs 的各种参数。结果表明，DTX-NPs 是单分散的纳米粒子，平均粒径为 158.50 ± 0.36nm，多分散指数为 0.36 ± 0.0，zeta 电位为 +18.30 ± 2.52mV，包封效率为 71.47 ± 5.62%。DTX-NPs 的药物释放符合 Korsmeyer-Peppas 模型，12 小时内约有 78%的药物释放。在针对叶酸受体的体外细胞毒性研究中，阳性 MDA-MBB-231 癌细胞显示出改善的细胞毒性，IC 为 0.58μg/mL，与多西紫杉醇（DTX）相比显著降低。体外渗透增强显示出 0.99 的外排比，表明药物成功穿过肠道。口服生物利用度显著提高，C 和 AUC 均高于 DTX 混悬液。总的来说，这些结果表明 DTX-NPs 可以作为口服药物递送的有前途的载体进行探索。
