TRIGGERABLE PLASMALOGEN LIPOSOMES - IMPROVEMENT OF SYSTEM EFFICIENCY

A photoactivated liposome release system that is generally applicable for triggered release of encapsulated hydrophilic materials is describ ed. This approach to phototriggered release, derived from the known ef fects of plasmalogen photooxidation on membrane permeability in whole cells and model membrane systems, relies on producing a lamellar phase change or increase in permeability upon cleaving its constitutive lip ids to single-chain surfactants using 630-820 nm light to sensitize th e photooxidation of the plasmalogen vinyl ether linkage. Semi-syntheti c plasmenylcholine liposomes containing encapsulated calcein and a mem brane-bound sensitizer, such as zinc phthalocyanine, tin octabutoxypht halocyanine, or bacteriochlorophyll a, were prepared by extrusion. irr adiation of air-saturated liposome solutions enhanced membrane permeab ility toward calcein and Mn2+, and promoted membrane fusion processes compared to non-irradiated or anaerobic controls. Bacteriochlorophyll a sensitization produced the fastest observed photoinitiated release r ate from these liposomes (100% calcein release in less than 20 min; 80 0 nm irradiation at 300 mW); the observed release rate was two orders of magnitude slower for egg lecithin liposomes prepared and irradiated under identical experimental conditions. Liposome aggregation, interl ipidic particle formation, and membrane fusion between adjoining lipos omes was observed by P-31-NMR, freeze-fracture/freeze-etch TEM, and cr yo-TEM as a function of irradiation time. The use of near-infrared sen sitizers and the capacity of photolyzed plasmenylcholine liposomes to undergo membrane fusion processes make photodynamic therapy with these liposome-borne sensitizers an attractive adjunct to biochemical targe ting methods.