Surface structured liposomes for site specific delivery of an antiviral agent-indinavir

Abstract

The present investigation was aimed at targeting indinavir, a protease inhibitor to cells of mononuclear phagocyte system (MPS) via mannosylated liposomes. β-d-1-thiomannopyranoside residues were covalently coupled with dimyristoyl phosphatidylethanolamine (DMPE) to generate mannosylated-DMPE (Man-DMPE) conjugate which was further incorporated with disteroyl phosphatidyl choline and cholesterol to prepare mannosylated liposomes. The optimized mannosylated liposomes were nanometric in size (142 ± 2.8 nm) with optimum entrapment efficiency (88.7 ± 2.3%). Less than 20% cumulative drug release was observed from the prepared formulations in 24 h in phosphate buffer saline (pH 7.4). Cellular uptake studies performed on J774.A1 macrophage cell line via flow cytometric analysis depicted enhanced uptake of mannosylated liposomes as compared to plain liposomes. Annexin-V-fluorescein isothiocyanate/propidium iodide apoptosis assay delineated marginal cytotoxicity in macrophages from the developed formulation. Plasma and tissue distribution studies performed to assess the drug reach to macrophage rich regions depicted a significant level (P < 0.05) of indinavir in macrophage rich tissues like liver, spleen, and lungs from mannosylated liposomes as compared to plain liposomes and free drug. The conducted studies suggest the potential of indinavir loaded mannosylated liposomes for anti-human immunodeficiency virus therapy.