Rapid release of liposomal contents upon photoinitiated destabilization with UV exposure.
The use of liposomes for the delivery of therapeutic agents to tumor sites took a major step forward with the introduction of sterically stabilized liposomes (polyethylene glycol [PEG]-liposomes). Several research groups reported the increased localization of PEG-liposomes at tumor sites. Once PEG-liposomes reach these sites, it can be desirable to increase the rate of release of encapsulated compound(s). The use of radiation for this purpose is attractive, because it can be delivered in a spatially and temporally selective manner. An effective strategy for the photoperturbation of PEG-liposomes relies on the photoinitiated polymerization of reactive lipids in the liposomal bilayer. Previous studies indicated that the inclusion of the photoreactive 1,2-bis[10-(2',4'-hexadienoyloxy)decanonyl]-sn-glycero-3-phosphocholine (bis-SorbPC(17,17)) among the lipids of PEG-liposomes had little effect on their permeability until the PEG-liposomes were exposed to UV light. Photoexposure increased the permeability of the PEG-liposomes 200-fold [Biochim. Biophys. Acta 1511 (2001) 113]. Further study of this phenomena has now revealed that PEG-liposomes can be designed that have extremely low permeabilities to water-soluble fluorescent probes at 37 degrees C in the dark, yet the permeability can be increased 28000-fold upon UV irradiation. The large increase in the rate of photoinitiated release of the encapsulated contents may be a consequence of increased phase separation between photoreactive and saturated phospholipids used in the PEG-liposomes.
Spratt
Tony
T
Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA. tony_spratt_phd@hotmail.com
Bondurant
Bruce
B
O'Brien
David F
DF
D002152:Calorimetry, Differential Scanning; D016503:Drug Delivery Systems; D008081:Liposomes / Q000737:chemistry / Q000528:radiation effects*; D015394:Molecular Structure; D010539:Permeability / Q000528:radiation effects; D010714:Phosphatidylethanolamines; D010777:Photochemistry; D011092:Polyethylene Glycols; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays
D008081:Liposomes; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols