The long-term goal of the project is to develop drugs for the prevention and treatment of adenoviral ocular disease. Although usually acute, they can become chronic and impair vision. Cidofovir is a nucleoside analog with activity against adenovirus, but is taken up poorly by cells. The focus of the application is to demonstrate the feasibility of optimizing the conjunctival uptake of cidofovir through derivitization into prodrugs that are substrates for the dipeptide transporter. This research will demonstrate the feasibility of improving the ocular absorption of topically applied polar drugs of low molecular weight via amino acid ester prodrug derivitization. By shifting the pathway of absorption from paracellular to transcellular, it will be possible to increase the probability of drug exposure of corneal and conjunctival epithelial cells.
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