In recent years several groups have described methods to prepare and utilize poly(ethylene glycol) conjugated phosphatidylethanolamine (PEG-PE) to sterically stabilize liposomes in order to avoid uptake of the liposomes by the reticuloendothelial system and increase their period of circulation. Sterically stabilized liposomes (PEG-liposomes) preferentially accumulate in the interstitium of tumor sites. If PEG-liposomes are to be effective for delivery of therapeutic agents, their drug permeability must be low enough that little passive release occurs during the time the liposomes are circulating in the bloodstream. However, once PEG-liposomes reach tumor sites, slow passive release of the encapsulated drug may not be optimal. Therefore, it is important to find methods to trigger the release of agents from suitably designed PEG-liposomes. The photoinduced destabilization of liposomes offers an attractive method to couple the temporal and spatial control of light to drug delivery. Bondurant and O'Brien [J. Am. Chem. Soc. 1998, 120, 13541-13542] showed that UV-induced cross-linking of lipids could destabilize certain PEG-liposomes and increase the bilayer permeability by greater than 102. Here we show that photochemical-induced destabilization of PEG-liposomes can be sensitized to visible light by the incorporation of a cyanine dye into the bilayer wall of PEG-liposomes. These observations demonstrate that light of wavelengths suitable for photodynamic therapy can also be used to increase the permeability of appropriately designed liposomes.
|Number of pages||6|
|State||Published - Jun 27 2000|