Bortezomib (BTZ), a proteasome inhibitor, is clinically used for the treatment of multiple myeloma and mantle cell lymphoma via intravenous or subcutaneous administration. Since BTZ has limited intestinal permeability, in this study, solid lipid nanoparticles (SLNs) were selected as lipid carrier to improve the intestinal permeability of BTZ. The nanoparticles were prepared by hot oil-in-water emulsification method and characterized for physicochemical properties. Moreover, in situ single-pass intestinal perfusion technique was used for intestinal permeability studies. Mean particle size of the BTZ-loaded solid lipid nanoparticles (BTZ-SLNs) was 94.6 ± 0.66 nm with a negative surface charge of -18 ± 11 mV. The entrapment efficiency of the BTZ-SLNs was 68.3 ± 3.7% with a drug loading value of 0.8 ± 0.05%. Cumulative drug release (%) over 48 h, indicated a slow release pattern for nanoparticles. Moreover, the SEM image showed a spherical shape and uniform size distribution for nanoparticles. Also, FTIR analysis indicated that BTZ was successfully loaded in the SLNs. The results of the intestinal perfusion studies revealed an improved effective permeability for BTZ-SLNs with a Peff value of about threefold higher than plain BTZ solution.
Keywords: Bortezomib; intestinal permeability; solid lipid nanoparticles.