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Advances in Pharmacological Sciences
Volume 2013, Article ID 915159, 9 pages
http://dx.doi.org/10.1155/2013/915159
Research Article

Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro

1Towson University Herpes Virus Lab, Department of Biological Sciences, Towson University, Towson, MD 21252, USA
2McDaniel College, Department of Biology, Westminster, MD 21157, USA
3Georgetown and George Mason University, Advanced Biomedical Science Graduate Certificate Program, Manassas, VA 20110, USA
4Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5Molecular Biology, Biochemistry, and Bioinformatics Program, Towson University, Towson, MD 21252, USA
6Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

Received 13 March 2013; Accepted 8 July 2013

Academic Editor: Thérèse Di Paolo-Chênevert

Copyright © 2013 Carol L. Berkower et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Following initial infection, herpesviruses retreat into a permanent latent state with periodic reactivation resulting in an enhanced likelihood of transmission and clinical disease. The nucleoside analogue acyclovir reduces clinical symptoms of the three human alpha herpesviruses, HSV-1, HSV-2, and VZV. Long-term administration of acyclovir (ACV) can reduce the frequency and severity of reactivation, but its low bioavailability and short half-life require a daily drug regimen. Our lab is working to develop a subcutaneous delivery system to provide long-lasting, sustained release of ACV. Previously, we demonstrated that an implantable silicone (MED-4050) device, impregnated with ACV protected against HSV-1 both in vitro and in vivo. Here, we extend our in vitro observations to include protection against both HSV-2 and VZV. We also demonstrate protection against HSV-2 in vitro using MED-4750, a silicone polymer designed for long-term use in humans. When release of ACV from MED-4750 is quantitated on a daily basis, an initial burst of 5 days is observed, followed by a long period of slow release with near-zero-order kinetics, with an average daily release of 1.3923 ± 0.5908 μg ACV over days 20–60. Development of a slow-release implant has the potential to significantly impact the treatment of human alpha herpesvirus infections.