Membrane permeability and stability in buffer and in human serum of fluorinated di-O-alkylglycerophosphocholine-based liposomes

The stability (with respect to encapsulated carboxyfluorescein release) of liposomes made from various fluorocarbon 1,2- or 1,3-di-O-alkylglycerophosphocholines (ether-connected) and their membrane permeability have been investigated in buffer and in human serum. Membranes and liposomes, whether formulated with fluorocarbon/fluorocarbon or mixed fluorocarbon/hydrocarbon, 1,2- or 1,3-di-O-alkylglycerophospholipids, display lower permeability coefficients and are able to retain more efficiently encapsulated CF, even when incubated in human serum, than any of their conventional counterparts. These fluorinated liposomes are as stable as the first generation of liposomes formulated with their fluorocarbon ester-connected 1,2-di-O-acylglycerophosphocholine analogs. These results further confirm that a fluorinated intramembranar layer reduces the permeability of membranes (more significantly when they are in a fluid state), protects them from the destabilizing effects of serum components and increases even the stability of the fluorinated liposomes whose membranes are in the gel state when incubated in human serum. The impact of the modular structure of the fluorinated phospholipids (number of fluorocarbon chains, ether vs. ester bond, 1,2- vs. 1,3-isomer, etc...) and structure/permeability/stability relationships are also presented.