A multistage oral delivery system of PTX for improving oral bioavailability and enhancing anticancer efficacy
A multistage oral delivery system of PTX for improving oral bioavailability and enhancing anticancer efficacy
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DOI：
10.1080/03639045.2021.1879831
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发表时间：
2021-02
影响因子：
3.4
通讯作者：
Ting Zhao;Hongli Zhou;Wanyan Wu;Xu Song;T. Gong
中科院分区：
文献类型：
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作者：
Ting Zhao;Hongli Zhou;Wanyan Wu;Xu Song;T. Gong
摘要目的溴粉防己碱（W 198）是一种P-糖蛋白（P-gp）抑制剂。目的制备紫杉醇（PTX）后口服W198胶束（W198/PTX胶束），以提高PTX的临床应用水平。意义紫杉醇多级口服给药系统可改善紫杉醇的水溶性差、肠道通透性差和多药耐药性。方法采用水浴超声法制备新型W198/PTX口服胶束，并在4 T1荷瘤小鼠模型上进行体内外评价。结果制得的PTX胶束和W198胶束圆整均匀。与未给药组相比，W198胶束预给药组对Caco-2细胞的PTX摄取效率更高，对4 T1细胞的毒性更明显。W198/PTX胶束组的口服生物利用度比仅PTX胶束组高近5.7倍。此外，W198/PTX胶束显示出增强的抗癌功效。结论我们建立了紫杉醇的多级口服给药系统，以提高紫杉醇的口服生物利用度和抗癌效果。
Abstract 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 in vivo and in vitro 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.