Triggered release of hydrophilic agents from plasmalogen liposomes using visible light or acid

Triggered release from liposomes composed of semi-synthetic 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphocholine (plasmalogen) lipids has been demonstrated using either aerobic visible illumination or low pH to induce leakage. The photodynamic release system consists of three functional components: (1) small (less than 1000 A) unilamellar plasmalogen vesicles (SUVs) containing encapsulated glucose, (2) oxygen and (3) zinc phthalocyanine (ZnPc) incorporated within the hydrophobic region of the SUV membrane. Irradiation (lambda greater than 640 nm) at 37 degrees C of air-saturated 1-alk-1'-enyl-2-palmitoyl-sn-glycero-3-phosphocholine (PlasPPC)/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) (8:1, mol/mol) liposomes at physiologically relevant temperatures results in glucose release rates that are twice those of the corresponding dark control. Photolysis of argon-saturated PlasPPC/DPPC liposomes or of identical vesicles lacking either ZnPc or the plasmalogen vinyl ether bond exhibit glucose release curves which are indistinguishable from the dark control. Irradiation under identical conditions, but in the presence of 100 mM sodium azide, also results in no increased rate of glucose release above that of the dark control. TLC analysis indicates that oxidized lipid species are produced only in air-saturated, irradiated plasmalogen liposomes. The acid lability of the plasmalogen vinyl ether linkage has also been used to trigger release of entrapped calcein. At pH 4.2, the release rate at 37 degrees C is increased 4-fold over rates observed at pH 8. TLC analysis indicates formation of a lysoplasmalogen product. Taken together, these results indicate that both photodynamic and acid triggering can be used to increase plasmalogen liposome permeability and suggest that these liposomes are potentially useful for drug delivery applications.