用于提高口服生物利用度和增强抗癌疗效的多阶段口服 PTX 递药系统。
A multistage oral delivery system of PTX for improving oral bioavailability and enhancing anticancer efficacy.
机构信息
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, P. R. China.
Institute of Regulatory Science for Medical Devices, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, P. R. China.
出版信息
Drug Dev Ind Pharm. 2021 Feb;47(2):259-267. doi: 10.1080/03639045.2021.1879831. Epub 2021 Feb 1.
OBJECTIVE
Bromotetrandrine (W198) was reported as a P-glycoprotein (P-gp) inhibitor. We aimed to prepare oral W198 micelles following by paclitaxel (PTX) micelles (W198/PTX micelles) to improve the clinical application of PTX.
SIGNIFICANCE
The poor water solubility, intestinal permeability, and multidrug resistance (MDR) of PTX can be improved in the multistage oral delivery system.
METHODS
The novel W198/PTX oral micelles were developed by water-bath ultrasound method and were evaluated and in 4T1 orthotopic tumor-bearing mice model.
RESULTS
PTX micelles and W198 micelles were prepared to be round and uniform. W198 micelles pre-administrated group showed higher cellular uptake efficiency of PTX on Caco-2 cells and more prominent cytotoxicity compared with W198-untreated group on 4T1 cells. The oral bioavailability of W198/PTX micelles group was nearly 5.7-folds higher than the PTX micelles only group. In addition, W198/PTX micelles showed enhanced anticancer efficacy.
CONCLUSIONS
We established a multistage oral delivery system to improve oral bioavailability and anticancer efficacy of PTX.
目的
溴代苦参碱（W198）被报道为一种 P 糖蛋白（P-gp）抑制剂。我们旨在制备口服 W198 胶束，随后是紫杉醇（PTX）胶束（W198/PTX 胶束），以改善 PTX 的临床应用。
意义
多阶段口服递药系统可改善 PTX 的水溶性差、肠道通透性差和多药耐药（MDR）。
方法
采用水浴超声法制备新型 W198/PTX 口服胶束，并在 4T1 原位荷瘤小鼠模型中进行评价。
结果
成功制备了圆整均一的 PTX 胶束和 W198 胶束。W198 胶束预处理组在 Caco-2 细胞上显示出更高的 PTX 细胞摄取效率，并且在 4T1 细胞上与未处理的 W198 组相比具有更显著的细胞毒性。W198/PTX 胶束组的口服生物利用度几乎是 PTX 胶束组的 5.7 倍。此外，W198/PTX 胶束显示出增强的抗癌疗效。
结论
我们建立了多阶段口服递药系统，以提高 PTX 的口服生物利用度和抗癌疗效。
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