Drug-Free Liposomes Containing Mannosylated Ligand for Liver-Targeting: Synthetic Optimization, Liposomal Preparation, and Bioactivity Evaluation.

Abstract

This research was performed to optimize the enzymatic synthesis of mannosylated ligand with which to prepare mannosy-lated liposomes and investigate their bioactivity. Based on single-factor studies, lipase dose, substrate molar ratio (diester lauric diacid-cholesterol to mannose) and temperature were identified as significant parameters, and optimal reaction conditions were determined through response surface methodology (RSM) with central composite design. The optimum operating parameters, 61.23 mg of lipase, a substrate molar ratio of 5.36, and 56.64 °C temperature offered a predicted yield (71.11%) which was consistent with the actual yield (69.08%). Drug-free mannosylated liposomes were prepared film-dispersion. The characterizations of these liposomes showed that mannosylated liposomes were well-dispersible spherical particles with an average particle size of 142.3 nm, the polydispersity index of 0.16, and a zeta potential of -19.8 mV. Pyrogen examination, hemolytic studies and cytotoxicity assays revealed no substantial safety concern for drug-free mannosylated liposomes. Cellular uptake efficiency of mannosylated liposomes by HepG2 cells was significantly higher than that of unmodified liposomes, demonstrating that mannosylated ligands have a positive effect on liver targeting. Overall, mannosylated liposomes could be active drug delivery system for combatting the therapy of hepatic diseases.