Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro
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...
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Series: | Advances in Pharmacological Sciences |
Online Access: | http://dx.doi.org/10.1155/2013/915159 |
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doaj-642c78e49f4c4d6d9145425894834b962020-11-25T03:29:33ZengHindawi LimitedAdvances in Pharmacological Sciences1687-63341687-63422013-01-01201310.1155/2013/915159915159Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In VitroCarol L. Berkower0Nicole M. Johnson1Stephen B. Longdo2Shenika O. McGusty-Robinson3Samantha L. Semenkow4Barry J. Margulies5Towson University Herpes Virus Lab, Department of Biological Sciences, Towson University, Towson, MD 21252, USATowson University Herpes Virus Lab, Department of Biological Sciences, Towson University, Towson, MD 21252, USATowson University Herpes Virus Lab, Department of Biological Sciences, Towson University, Towson, MD 21252, USATowson University Herpes Virus Lab, Department of Biological Sciences, Towson University, Towson, MD 21252, USATowson University Herpes Virus Lab, Department of Biological Sciences, Towson University, Towson, MD 21252, USATowson University Herpes Virus Lab, Department of Biological Sciences, Towson University, Towson, MD 21252, USAFollowing 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.http://dx.doi.org/10.1155/2013/915159 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carol L. Berkower Nicole M. Johnson Stephen B. Longdo Shenika O. McGusty-Robinson Samantha L. Semenkow Barry J. Margulies |
spellingShingle |
Carol L. Berkower Nicole M. Johnson Stephen B. Longdo Shenika O. McGusty-Robinson Samantha L. Semenkow Barry J. Margulies Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro Advances in Pharmacological Sciences |
author_facet |
Carol L. Berkower Nicole M. Johnson Stephen B. Longdo Shenika O. McGusty-Robinson Samantha L. Semenkow Barry J. Margulies |
author_sort |
Carol L. Berkower |
title |
Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro |
title_short |
Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro |
title_full |
Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro |
title_fullStr |
Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro |
title_full_unstemmed |
Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro |
title_sort |
silicone-acyclovir controlled release devices suppress primary herpes simplex virus-2 and varicella zoster virus infections in vitro |
publisher |
Hindawi Limited |
series |
Advances in Pharmacological Sciences |
issn |
1687-6334 1687-6342 |
publishDate |
2013-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2013/915159 |
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