Triggerable plasmalogen liposomes: improvement of system efficiency.

A photoactivated liposome release system that is generally applicable for triggered release of encapsulated hydrophilic materials is described. This approach to phototriggered release, derived from the known effects 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 lipids to single-chain surfactants using 630-820 nm light to sensitize the photooxidation of the plasmalogen vinyl ether linkage. Semi-synthetic plasmenylcholine liposomes containing encapsulated calcein and a membrane-bound sensitizer, such as zinc phthalocyanine, tin octabutoxyphthalocyanine, or bacteriochlorophyll a, were prepared by extrusion. Irradiation of air-saturated liposome solutions enhanced membrane permeability 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 rate from these liposomes (100% calcein release in less than 20 min; 800 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, interlipidic particle formation, and membrane fusion between adjoining liposomes was observed by 31P-NMR, freeze-fracture/freeze-etch TEM, and cryo-TEM as a function of irradiation time. The use of near-infrared sensitizers 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 targeting methods.