Liposomes and tear fluid. I. Release of vesicle-entrapped carboxyfluorescein.

The successful application of liposomes as a topical ophthalmic drug delivery device requires knowledge of vesicle stability in the presence of tear fluid. The release of 5-carboxyfluorescein from large unilamellar liposomes in the presence of rabbit tear fluid was studied in vitro as a function of bilayer cholesterol content. Reverse evaporation vesicles were prepared from egg phosphatidylcholine, stearylamine and varying amounts of cholesterol. Both the rate and the extent of fluorescent dye release were significantly increased in the presence of rabbit tear fluid at all cholesterol levels. However, by incorporating increasing amounts of cholesterol in the vesicle bilayers, tear-induced leakage was reduced. The release kinetics reported in this study are similar to those observed in the presence of human serum. While serum-induced leakage is attributed to high-density lipoprotein-mediated destabilization, reported differences in tear protein composition suggest some other, as yet unidentified, factor.