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Open Access Research

Controlled release delivery of penciclovir via a silicone (MED-4750) polymer: kinetics of drug delivery and efficacy in preventing primary feline herpesvirus infection in culture

Samantha L Semenkow125, Nicole M Johnson1, David J Maggs3 and Barry J Margulies1246*

Author Affiliations

1 Towson University Herpes Virus Lab, Department of Biological Sciences, Towson University, Towson, MD 21252, USA

2 Molecular Biology, Biochemistry, and Bioinformatics Program, Towson University, Towson, MD 21252, USA

3 Department of Surgical and Radiological Sciences, University of California, Davis, Davis, CA 95616, USA

4 Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

5 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

6 Department of Biological Sciences, Towson University, Towson MD 21252, USA

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Virology Journal 2014, 11:34  doi:10.1186/1743-422X-11-34

Published: 22 February 2014

Abstract

Background

Herpesviruses are ubiquitous pathogens that infect and cause recurrent disease in multiple animal species. Feline herpesvirus-1 (FHV-1), a member of the alphaherpesvirus family, causes respiratory illness and conjunctivitis, and approximately 80% of domestic cats are latently infected. Oral administration of famciclovir or topical application of cidofovir has been shown in masked, placebo-controlled prospective trials to reduce clinical signs and viral shedding in experimentally inoculated cats. However, to the authors’ knowledge, other drugs have not been similarly assessed or were not safe or effective. Likewise, to our knowledge, no drugs have been assessed in a placebo-controlled manner in cats with recrudescent herpetic disease. Controlled-release devices would permit long-term administration of these drugs and enhance compliance.

Methods

We therefore engineered implantable cylindrical devices made from silicone (MED-4750) impregnated with penciclovir, for long-term, steady-state delivery of this drug.

Results

Our data show that these devices release penciclovir with a burst of drug delivery until the tenth day of release, then at an average rate of 5.063 ± 1.704 μg per day through the next 50 days with near zero-order kinetics (in comparison to MED-4750-acyclovir devices, which show the same burst kinetics and average 2.236 ± 0.625 μg/day thereafter). Furthermore, these devices suppress primary infection of FHV-1 in a cell culture system.

Conclusions

The clinical deployment of these silicone-penciclovir devices may allow long-term treatment of FHV-1 infection with a single intervention that could last the life of the host cat.

Keywords:
Feline herpesvirus; Penciclovir; Silicone; Implant; Ocular; Controlled release; Herpetic disease