Liposomal drug delivery for solubility and bioavailability enhancement of efavirenz

Abstract

To overcome the limited solubility and low bioavailability of efavirenz a liposomal drug delivery system was formulated using thin film hydration technique. Optimal ratios of total lipid blend:drug, soya lecithin:cholesterol and polyethylene glycol 400 concentration were determined using Box-Behnken design with vesicle size and entrapment efficiency as responses. The optimized liposomal dispersions were characterized by vesicle size, entrapment efficiency, transmission electron microscopy, in vitro drug release and in vivo pharmacokinetics. The vesicle size was found to be in range of 694.5-1200.0 nm and entrapment efficiency was above 80 %. Statistical studies revealed that vesicle size and entrapment efficiency increased with increase in total lipid blend:drug and polyethylene glycol 400 concentration. Transmission electron microscopy showed that unilamellar and multi-lamellar vesicles were formed. Optimized liposomal dispersion was solidified using nanosponges. Solid liposomes were characterized by micromeritics, differential scanning calorimetry, Fourier-transform infrared spectroscopy and bioavailability. As compared to plain drug a 10-fold increase in percent release was observed in 6 h in liposomal preparation. In vivo pharmacokinetic studies revealed that bioavailability increases 2 folds as compared to plain drug. Lipid-based drug delivery like liposomes are taken up through lymphatic pathway. Since the human immunodeficiency virus settles in lymphoid organs, lymphatic drug delivery can be advantageous in the treatment of acquired immune deficiency syndrome. Thus, the pharmacokinetic studies demonstrated that efavirenz-loaded liposomes could significantly upgrade the solubility and oral bioavailability of efavirenz and improve the therapeutic efficacy.