Enhancement of the intestinal absorption of bortezomib by self-nanoemulsifying drug delivery system

Abstract

Purpose: Intestinal drug absorption is one of the main factors that govern the fraction of oral dose absorbed (Fa) of drugs. It is reported that oral absorption of bortezomib (BTZ) can be restricted by its low intestinal permeability. In this study, we aimed to evaluate the impact of self-nanoemulsifying drug delivery systems (SNEDDS) on the intestinal absorption and Fa of BTZ.Methods: Intestinal permeability studies were conducted using in situ single-pass intestinal perfusion (SPIP) technique in rats. Human intestinal absorption (Peff (Human)) and Fa values of BTZ and BTZ-SNEDDS were predicted based on SPIP data.Results: Based on the obtained data, Peff (rat) values of (3.36 ± 0.5) × 10−5 and (8.9 ± 3) × 10−5 cm/s (mean ± SEM) were calculated for BTZ and BTZ-SNEDDS, respectively. Meanwhile, Peff (human) values of (7 × 10−5) and (68 × 10−5) cm/sec were predicted for BTZ and BTZ-SNEDDS, respectively. Besides, Fa (human) values of 72.5 and 97% were estimated for BTZ and BTZ-SNEDDS, respectively.Conclusions: According to the obtained data, it is concluded that SNEDDS can be considered as a promising drug delivery system to improve the intestinal absorption and Fa values of BTZ.