LONG-TERM THERAPY FOR HERPES RETINITIS IN AN ANIMAL-MODEL WITH HIGH-CONCENTRATED LIPOSOME-ENCAPSULATED HPMPC

Objective: To evaluate (s)-1-(3-hydroxy-2-phosphonyl methoxypropyl) cy tosine (HPMPC), a potent antiherpes and anticytomegalovirus drug, as a long-term treatment of experimental retinitis in rabbits. Methods: Th e drug was first encapsulated into a liposome delivery system in three different concentrations and injected intravitreally. Sequentially, t he highest concentration that was shown to be nontoxic to the retina w as evaluated in a model of retinitis at 60, 90, 120, 170, and 240 days , after which herpes simplex virus type 1 was inoculated onto the reti nal surface. Results: A dose of 1000 mu g of HPMPC encapsulated in lip osomes gives a protective effect for up to 8 months. Conclusions: Redu ced toxic effects and longer-term efficacy compared with free drug was observed. Given the 50 times higher activity of HPMPC against human c ytomegalovirus than herpes simplex virus type 1, a single injection of 1000 mu g of liposome-encapsulated HPMPC may have a very prolonged ef fect in the treatment of cytomegalovirus retinitis.