Preparation and evaluation of the intestinal permeability of bortezomib nanoemulsion and solid lipid nanoparticles

Abstract

Introduction: Bortezomib (BTZ) is used for the treatment of multiple myeloma and mantle cell lymphoma via intravenous or subcutaneous administration. It seems that the low intestinal absorption of BTZ can be an important challenge for the oral dosage formulation of BTZ. Purposes: The main goal of this study was evaluating the intestinal absorption of BTZ and assessing the impact of the lipid-based drug delivery systems: solid lipid nanoparticles (SLNs) and self-nanoemulsifying drug delivery systems (SNEDDS), on the intestinal permeability and fraction of oral dose absorbed of BTZ. Methods: Rat effective intestinal permeability (Peff (rat)) values of the formulations were determined using in situ single-pass intestinal perfusion (SPIP) technique. In addition human intestinal absorption (Peff (human)) values of the formulations were predicted based on the obtained Peff (rat) values. Besides, human fraction of oral dose absorbed (Fa (human)) values of the formulations were estimated based on the reported correlation between Peff (rat) and Fa (human) Results: Based on the obtained data, Peff (rat) values of (3.36 ± 0.5) × 10-5, (8.9 ± 3) × 10-5, and (10.4 ± 2) × 10-5 cm/sec (mean ± SEM) were calculated for BTZ, BTZ-loaded SNEDDS, and BTZ-loaded SLNs, respectively. Meanwhile, Peff (human) values of (7 × 10-5) and (68 × 10-5), and (85 × 10-5) cm/sec were predicted for BTZ, BTZ-loaded SNEDDS, and BTZ-loaded SLNs, respectively. In addition, Fa (human) values of 72.5%, 97%, and 98% were estimated for BTZ, BTZ-loaded SNEDDS, and BTZ-loaded SLNs, respectively. Conclusion: According to the obtained data, it is concluded that SNEDDS and SLNs can be considered as mighty drug delivery systems to promote the intestinal absorption and Fa of BTZ.