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May 1995

Long-term Therapy for Herpes Retinitis in an Animal Model With High-Concentrated Liposome-Encapsulated HPMPC

Author Affiliations

From the Department of Ophthalmology, University of California—San Diego, La Jolla (Drs Besen, Flores-Aguilar, Kupperman, Gangan, and Freeman, and Messrs Munguia, Vuong, and Bergeron-Lynn); The Anheuser Busch Eye Institute of St Louis (Mo) University (Dr Assil and Mr Pursley); Rega Institute of Medical Research, Leuven, Belgium (Dr De Clercq); and the Division of Biometry, Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles (Dr Azen).

Arch Ophthalmol. 1995;113(5):661-668. doi:10.1001/archopht.1995.01100050129042

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 μg 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 I, a single injection of 1000 μg of liposome-encapsulated HPMPC may have a very prolonged effect in the treatment of cytomegalovirus retinitis.