Bioenhanced Polymeric Nanoparticulate Compositions of an Anti-Tubercular-Anti-HIV Drug Combination

The present study reports the role of the nanoparticulate drug delivery systems of rifampicin-lopinavir combinations on enhanced bioavailability of the drugs following oral administration. Entrapping both drugs in the ratio 1:1 is an additional objective. Poly (ethylene sebacate), a novel hydrolytically stable, nonionic, biocompatible and biodegradable, non-mutagenic and non-genotoxic polymer was selected for the study. PLGA and PLA were selected for comparative evaluation. Nanoparticles with adequate drug loading and particle size 350-450nm were developed and freeze dried using a combination of trehalose and lutrol-f-68 as cryoprotectant and characterized for zeta potential, hydrophobicity, SEM, DSC, pXRD etc. Nanoparticles found to be stable as per ICH guidelines. Pharmacokinetic evaluation of RIF-LOPI PES and PLGA nanoparticles revealed comparable plasma drug concentration, delayed Tmax and enhanced oral bioavailability, PLA nanoparticle revealed significantly higher bioavailability. T1/2 values were significantly higher with the nanoparticles for both RIF and LOPI. Following oral administration revealed high concentration of drugs in the RES organs lungs, liver and spleen compared to plain drugs was observed. The high bioavailability of both RIF and LOPI confirms the ability of nanoparticles both to enhance drug absorption and also provide protection in vivo. This protective effect of the nanoparticles enabled high bioavailability of LOPI despite being in combination with RIF an inducer of cytochrome P450.