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-alkylgl ycerophosphocholines (ether-connected) and their membrane permeability have been investigated in buffer and in human serum. Membranes and li posomes, whether formulated with fluorocarbon/fluorocarbon or mixed fl uorocarbon/hydrocarbon, 1,2- or 1,3-di-O-alkylglycerophospholipids, di splay lower permeability coefficients and are able to retain more effi ciently 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 flu orocarbon 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 ar e in a fluid state), protects them from the destabilizing effects of s erum components and increases even the stability of the fluorinated li posomes whose membranes are in the gel state when incubated in human s erum. The impact of the modular structure of the fluorinated phospholi pids (number of fluorocarbon chains, ether vs. ester bond, 1,2- vs. 1, 3-isomer, etc...) and structure/permeability/stability relationships a re also presented.