Long-term therapy for herpes retinitis in an animal model with high-concentrated liposome-encapsulated HPMPC

G. Besen, M. Flores-Aguilar, K. K. Assil, B. D. Kupperman, P. Gangan, M. Pursley, D. Munguia, C. Vuong, E. De Clercq, G. Bergeron-Lynn and al. et
Department of Ophthalmology, University of California-San Diego, La Jolla, USA.

OBJECTIVE: To evaluate(s)-1-(3-hydroxy-2-phosphonyl methoxypropyl) cytosine (HPMPC), a potent antiherpes and anticytomegalovirus drug, as a long-term treatment of experimental retinitis in rabbits. METHODS: The drug was first encapsulated into a liposome delivery system in three different concentrations and injected intravitreally. Sequentially, the highest concentration that was shown to be nontoxic to the retina was 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 retinal surface. RESULTS: A dose of 1000 micrograms of HPMPC encapsulated in liposomes gives a protective effect for up to 8 months. CONCLUSIONS: Reduced toxic effects and longer-term efficacy compared with free drug was observed. Given the 50 times higher activity of HPMPC against human cytomegalovirus than herpes simplex virus type 1, a single injection of 1000 micrograms of liposome-encapsulated HPMPC may have a very prolonged effect in the treatment of cytomegalovirus retinitis.