Conjugated crown ether lipid liposomes: enhancing integrity in serum through novel surface modifications

This study explores the potential of 18-crown-6 ether to enhance liposomal integrity in biological media. A novel 1,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE)-crown ether conjugate was synthesized and incorporated into phosphatidylcholine/cholesterol liposomes at varying concentrations (0.5-8 mol%). The physicochemical characteristics, serum integrity, and response to divalent cations were systematically evaluated. Although, these crown ether-modified liposomes do not provide the same level of protection as PEGylation at 48 hours, they clearly exhibited improved integrity in serum at 24 hours compared to non-pegylated liposomes under the same conditions. Moreover, when exposed to calcium ions (5 mM), crown ether-modified liposomes maintained significantly greater stability levels at 24 h in comparison to unmodified liposomes. Furthermore, co-functionalization with both crown ether (2%) and PEG (2%) lipids resulted in stability identical to 4% PEGylated liposomes under the same conditions, suggesting an additive stabilization effect of crown ether and PEG, at least at the concentration applied. These findings introduce crown ether-modified liposomes as a novel approach to modulate liposome-protein interactions and potentially enhance drug delivery in physiological environments containing high concentrations of calcium.