Preparation of neo-galactosylated liposomes and their interaction with mouse peritoneal macrophages

Abstract

In order to target liposomes to cells expressing at their surface a galactose-binding site we have prepared liposomes containing new synthetic galactolipids. Neo-galactosylated liposomes were prepared by covalently coupling β- d-1-thiogalactopyranoside residues, substituted with a hydrophilic spacer-arm and functionalized with a sulfhydryl group, to preformed large unilamelar vesicles containing 4-( p-maleimidophenyl)butyryl phosphatidylethanolamine. The vesicles, having a galactose content above a threshold value of about 5 mol%, could be aggregated with Ricinus communis agglutinin. This aggregation was reversed by addition of excess free methyl β- d-galactopyranoside, indicating that the surface glucidic moieties of these liposomes were accessible to the lectin. Compared to the control vesicles, the neo-galactosylated liposomes (containing 15 mol% galactose) presented in vitro an increased binding to cells possessing a β- d-galactose specific receptor, i.e. resident mouse peritoneal macrophages. At 4°C, the specific binding was about 2-fold, whereas at 37°C it was increased to about 4–5-fold. This differential binding was largely unaffected by serum and, interestingly was much dependent on the degree of galactosylation of the liposomes, i.e. a threshold value of 5 mol% was needed to observe an increased binding of the targeted vesicles to the macrophages.