A self-microemulsion enhances oral absorption of Docetaxel by inhibiting P-glycoprotein and CYP metabolism

Abstract

Abstract Oral absorption of docetaxel was limited by drug efflux pump p-glycoprotein (P-gp) and cytochrome P450 enzyme (CYP 450). Therefore, co-loading agent that inhibits P-gp and CYP 450 in self-nanoemulsifying drug delivery system (SMEs) is considered as a promising strategy for oral delivery of docetaxel. In this study, curcumin was selected as an inhibitor of P-gp and CYP 450, and it was coencapsuled in SMEs to improve the oral bioavailability of docetaxel. SMEs quickly dispersed in water within 20 seconds, and the droplet size was 32.23 ± 2.21 nm. The release rate of curcumin from DC-SMEs was higher than that of docetaxel in vitro. Compared with free docetaxel, SMEs significantly increased the permeability of docetaxel by 4.6 times. And competitive experiments showed that the increased permeability was the result of inhibition of p-gp. The half-life and oral bioavailabilty of DC-SMEs increased about 1.7 times and 1.6 times than docetaxel SMEs, which indicated that its good pharmacokinetic behavior was releated to the restriction of hepatic first-pass metabolism. In conclusion, DC-SMEs was an ideal platform to facilitate oral delivery of docetaxel through inhibited P-gp and CYP 450.