The goal of our research is to evaluate an improved method of drug delivery to treat ocular disease caused by herpes simplex virus, (HSV) infection. We suggest that drug efficacy will be improved and its toxicity to normal cells of the cornea diminished if confined in high concentrations at the target area where it can be therapeutically effective. To achieve this, liposomes containing antiviral drugs will be constructed that express specific anti HSV antibody on their surface. Such immunoliposomes should attach specifically to virus infected cells and drug will permeate out in a high local concentration for a prolonged period so inhibiting viral replication close to the site of liposome attachment thus necessitating infrequent topical treatment of the eye. Liposomes will be prepared of varying physiochemical construction incorporating antiviral drug and expressing anti HSV antibody of different specifities. Such liposomes will be compared to free antiviral drug and several control liposomes for their effectiveness at controlling experimental herpetic dendritic and stromal keratitis in rabbits and mice. Experiments will be done to define the optimal physicochemical construction of immunoliposomes for in vivo treatment of keratitis, prevention of HSV latency, penetration of the cornea and protection against HSV infection in tissue culture systems. The results of our study may produce a vehicle for topical treatment of herpetic keratitis that is more effective than existing methods of treatment of stromal keratitis and may be effective when administered only once daily.
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