Lectin-mediated binding of liposomes and delivery of specific agents by this means to the ocular lens, cornea and other intraocular tissues will be investigated. Whole eyes and human, rabbit and rat ocular tissues will be used for in vitro studies and rabbits will be employed for in vivo experiments. Liposomes will be prepared from various lipid (and glycolipid) and fluorescein-labelled lectin combinations to assess the effects of liposomal charge on binding of lectin to the vesicles and on the binding of liposome-lectin complexes to ocular tissues. The effects of vesicle size and form on binding, trapping efficiency, tissue distribution, and intraocular pressure will also be evaluated. Binding will be assayed in vitro and in vivo by fluorescence microscopy (FM), and scanning and transmission electron microscopy. The fate of liposomes bound to ocular tissues over specific time intervals will also be evaluated. The effects of inclusion of cholesterol and dipalmitoylphosphatidyl-labelled compounds will be assessed by fluorescence spectroscopy and liquid scintillation counting of external aqueous phases of liposome suspensions at different time intervals. Intracellular and intratissue delivery of fluorescent markers by liposomes will be studied by FM, fluorescence spectroscopy and UV-visible slit lamp densitography. Delivery of isotope labelled markers will be analyzed by autoradiography and liquid scintillation counting of tissue homogenates. Liposomal delivery of 8-methoxypsoralen will be assessed by phosphorescence and EPR spectroscopy and other techniques. Free radical scavengers and aldose reductase inhibitors will be delivered to the ocular lens in vivo to evaluate their ability to protect the lens from the development of radiation and sugar cataracts, respectively, and any dose-response phenomena associated with them. Liposomally encapsulated pilocarpine and nucleic acid analogues will be applied to the cornea in vivo and the effects of liposomal delivery on diffusion of drugs across the cornea and on drug activity on the cornea itself will be evaluated. Pilot studies will also be carried out to assess the feasibility of using liposomally encapsulated proteolytic enzymes to lyse cataracts in situ.
