pH‐sensitive liposomes for receptor‐mediated delivery to chicken hepatoma (LMH) cells

Abstract

pH-sensitive liposomes composed of dioleoylphosphatidylethanolamine and cholesterol hemisuccinate (3:2 mol/mol) bearing the N-acetylglucosamine derivative of bovine serum albumin (N-Ac-BSA) were applied for receptor-mediated delivery in chicken hepatoma (LMH) cells expressing the N-Ac-BSA-binding asialoglycoprotein receptor. Fluorescently labeled dextran was entrapped in liposomes by a modified freeze-thawing method (encapsulation efficiency of 23%). A novel method of coupling proteins onto the surface of preformed liposomes yielded a coupling efficiency of 60-70%. The association of pH-sensitive and lecithin liposomes with LMH cells was monitored by fluorescence-activated cell sorting and confocal microscopy. Prerequisites for receptor-mediated delivery to LMH cells were both the pH sensitivity of liposomes and the presence of N-Ac-BSA on the liposomal surface.