At present, drugs and dyes are delivered to the eye mainly through topical and systemic routes. Topical delivery cannot yield high intraocular concentrations, and the systemic route is prone to side effects due to the exposure of the whole body. For dyes, the intravenous route is limited by the lack of definition and synchronicity with the cardiac cycle of the dye front and the inability to repeat the bolus delivery. The goal of this project is to develop a new drug delivery system that will allow controlled, repeated, and local delivery of substances specifically to the eye. This can be achieved by encapsulating the active substance in artificial vesicles, called liposomes injecting them intravenously, and lysing them at the target site by raising the temperature locally by 40C with a pulsed light source; this causes the local release of a high concentration of dye or drug. By solving some of the problems of present delivery systems this new modality may open new avenues in diagnosis and therapy, some of which will be evaluated in this study. By encapsulating carboxyfluorescein in liposomes at high concentrations, the fluorescence will be quenched, but when the dye is released and diluted in the blood, an intense fluorescence will be obtained. This fluorescence will allow us to follow the well-defined dye front as it progresses along the vasculature from the selected artery, through the arterioles and the capillary network, and into the veins. The fact that the dye front will be well-defined, present only in a selected branch of the retinal vasculature without background from the choroid, and obtained repeatedly will open new opportunities in fluorescein angiography. This will permit measurement of blood velocity, especially in the microcirculation, and blood flow in arterioles as well as repeated measurement before and after induced changes in physiological conditions. In addition, the measurement of the fluorescence after the passage of the bolus may allow assessment of local blood-retinal barrier dysfunction. The new delivery system also has important applications in therapy in the local delivery of drugs. Thrombolitic agents and vasodilators could be released next to an embolus to relieve branch vein or artery occlusions. Coagulating agents could be used to curtail neovascularization. The research will focus on instrumentation development for delivery, angiography, blood flow, and blood-retinal barrier measurements as well as on assessment in animals of the above potential applications.
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