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 (F_a) 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 F_a of BTZ.

Methods: Intestinal permeability studies were conducted using in situ single-pass intestinal perfusion (SPIP) technique in rats. Human intestinal absorption (P_{eff (Human)}) and F_a values of BTZ and BTZ-SNEDDS were predicted based on SPIP data.

Results: Based on the obtained data, P_{eff (rat)} values of (3.36 ± 0.5) × 10⁻⁵ and (8.9 ± 3) × 10⁻⁵cm/s (mean ± SEM) were calculated for BTZ and BTZ-SNEDDS, respectively. Meanwhile, P_{eff (human)} values of (7 × 10⁻⁵) and (68 × 10⁻⁵) cm/sec were predicted for BTZ and BTZ-SNEDDS, respectively. Besides, F_{a (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 F_a values of BTZ.

Keywords:

• Bortezomib
• SNEDDS
• SPIP
• intestinal absorption

Acknowledgments

The financial support from the ‘Drug Applied Research Center’, Tabriz University of Medical Sciences is greatly acknowledged. This paper is based on a PhD thesis (Dissertation number: 108) submitted by Mohammad Mahmoudian in Faculty of Pharmacy, Tabriz University of Medical Sciences.

Conflict of interests

The authors declare that there are no conflicts of interest.