Synthesis of mannose-cholesterol conjugates for targetedliposomal drug delivery

Several novel, mannose-cholesterol conjugates for use in targeted liposomal drug delivery were synthesized via a modular strategy utilizing the Cu(I)-catalysed Huisgen azide-alkyne cycloaddition (“Click”) reaction. The conjugates, which were fully characterized, comprised either a single mannose unit or a trivalent mannose cluster joined to cholesterol via bifunctional PEG-based linkers of different lengths. The neutral conjugates offer advantages over a previously reported cationic conjugate and the modular strategy employed can be readily adapted for the preparation of conjugates with alternative targeting groups.