A multistage oral delivery system of PTX for improving oral bioavailability and enhancing anticancer efficacy

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.

Keywords:

• Paclitaxel micelles
• W198 micelles
• oral bioavailability
• multidrug resistance
• breast cancer

Author contributions

TG, XS, and TZ designed research; TZ, HLZ, and WYW performed research; TZ, HLZ analyzed data; TZ and XS wrote the article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was financially supported by Sichuan Major Science and Technology Project on Biotechnology and Medicine [No. 2018SZDZX0018], Fundamental Research Funds for the Central Universities [No. 2017SCU12062] and China Postdoctoral Science Foundation [No. 2017M623051] and National Natural Science Foundation of China [NSFC, No. 32001002].