EVALUATION OF A NOVEL LIPID PRODRUG FOR INTRAOCULAR DRUG-DELIVERY - EFFECT OF ACYCLOVIR DIPHOSPHATE DIMYRISTOYLGLYCEROL IN A RABBIT MODEL WITH HERPES-SIMPLEX VIRUS-1 RETINITIS

Background: Acyclovir diphosphate dimyristoylglycerol is a lipid prodr ug of acyclovir that forms liposomes and provides substantial activity against herpes simplex virus, acyclovir-resistant strains of herpes s implex virus, and human cytomegalovirus. We therefore tested this prom ising new drug in a rabbit model of herpes simplex retinitis. Methods: A total of 22 pigmented rabbits were pretreated with either acyclovir diphosphate dimyristoylglycerol, ganciclovir, acyclovir, or buffer, R etinae then were inoculated with herpes simplex virus-1 or buffer 1 we ek after the injection of drug. In another experiment we compared the effects of acyclovir diphosphate dimyristoylglycerol and acyclovir dip hosphate dioleoylglycerol on the optical clarity of vitreous. Results: Animals injected intravitreally with acyclovir diphosphate dimyristoy lglycerol showed retinitis that was less severe than that in animals i njected with ganciclovir, acyclovir, and buffer; differences in gradin g scores of the retinitis between animals injected with acyclovir diph osphate dimyristoylglycerol and those injected with buffer were statis tically significant (P = 0.0015). Vitreous and optical media became cl ear 4 days after acyclovir diphosphate dioleoylglycerol injection comp ared with 10 days after with acyclovir diphosphate dimyristoylglycerol injections. Conclusion: Acyclovir diphosphate dimyristoylglycerol had prolonged antiviral activity against herpes simplex virus-1 retinitis in a rabbit model. This drug delivery system, modified to improve opt ical clarity, may allow long-acting intravitreal treatment of cytomega lovirus retinitis and other retinal diseases.