The feasibility of lectin-mediated liposomal drug delivery to the ocular lens for potential clinical and experimental applications will be assessed. Aldose reductase inhibitors (ARI) and free radical scavengers will be delivered to rabbit lenses in vivo in liposomes, employing miniosmotic pumps, and the efficacy of such delivery in inhibiting development of experimental sugar or UV-radiation induced cataracts will be monitored. Lenticular changes will be monitored in vivo by UV-visible slit lamp densitography and by histologic and spectroscopic (fluorescence, phosphorescence and UV-visible transmission) analyses of excised lenses. ARI delivered to lenses will be quantitated by spectroscopic methods we have developed and by assaying aldose reductase activity. Similar in vivo delivery will be utilized to examine the potential phototoxicities and/or photosensitizing properties of selected agents, including 8-methoxypsoralen, other psoralen derivatives, retinoids and certain antibiotics (e.g. adriamycin). Photoinduced lenticular changes will be monitored in vivo as above, and in vitro by fluorescence and phosphorescence of excised lenses. Further studies will be carried out to characterize in vitro and in vivo liposomal delivery of agents to the ocular lens. Determinations of amounts of agents delivered will employ liposomally encapsulated fluorescent, phosphorescent, 13C-enriched and radio-labeled agents, quantitated in lenses by fluorescence, phosphorescence and 13C NMR spectroscopy and liquid scintillation counting. The numbers of vesicles bound to the lens and the intratissue localization of agents delivered will be assessed by the same techniques, and by fluorescence and transmission electron microscopy and autoradiography. To examine types of vesicle-tissue interactions taking place, tissue localization of fluorescent-labeled lipids incorporated in vesicles will be examined by fluorescence microscopy. Influences of the vesicle size, form, lipid composition and total lipid dose administered on all parameters examined will be evaluated. Effects of in vivo liposome administration on all ocular tissues will be assessed, utilizing in vivo tonographic measurements and slit lamp examinations, and histologic analyses of excised tissues. Finally, in order to further develop liposomal delivery systems for selected intraocular structures, the specificities and extent of binding of different lectins and lectin-containing liposomes to the structures will continue to be screened.
