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.
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.
A dose of 1000 μg of HPMPC encapsulated in liposomes gives a protective effect for up to 8 months.
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 I, a single injection of 1000 μg of liposome-encapsulated HPMPC may have a very prolonged effect in the treatment of cytomegalovirus retinitis.
Besen G, Flores-Aguilar M, Assil KK, Kupperman BD, Gangan P, Pursley M, Munguia D, Vuong C, De Clercq E, Bergeron-Lynn G, Azen SP, Freeman WR. Long-term Therapy for Herpes Retinitis in an Animal Model With High-Concentrated Liposome-Encapsulated HPMPC. Arch Ophthalmol. 1995;113(5):661-668. doi:10.1001/archopht.1995.01100050129042