Current antiviral therapy for the human herpes viruses, HSV–1, –2, and varicella zoster virus and the feline herpesvirus, FHV-1, consists of multiple doses of FDA-approved anti-herpetic drugs (typically acyclovir [ACV], valacyclovir, penciclovir [PCV], or famciclovir) taken daily for the lifetime of the host. These daily doses require rigorous patient compliance; missed doses allow small windows of drug troughs that permit breakout replication, sometimes resulting in drug-resistant mutants. Our research involves slow, controlled release of ACV or PCV from both biodegradable and non-biodegradable polymer matrices. These devices release continuous, steady levels of drug for an estimated 3 to 5 years after a single implantation. We are continuing to explore the chemistry, biology, pharmacology, and engineering of these implants to further improve their design and eventual clinical deployment in human and veterinary patients.
Semenkow SL, Johnson NM, Maggs DJ, Margulies BJ. 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. Virol J 11:34 (2014).
Berkower CL, Johnson NM, Longdo SB, McGusty-Robinson SO, Semenkow SL, Margulies BJ. Silicone-acyclovir controlled release devices suppress primary herpes simplex virus-2 and varicella zoster virus infections in vitro. Adv Pharmacol Sci 2013:915159 (2013).
Johnson TP, Frey R, Modugno M, Brennan TP, Margulies BJ. Development of an aciclovir implant for the effective long-term control of herpes simplex virus type-1 infection in Vero cells and in experimentally infected SKH-1 mice. Int J Antimicrob Agents 30:428-35 (2007).
Margulies BJ, Gibson W. The chemokine receptor homologue encoded by US27 of human cytomegalovirus is heavily glycosylated and is present in infected human foreskin fibroblasts and enveloped virus particles. Virus Res 123:57-71 (2007).
Bonavia A, Bullock BT, Gisselman KM, Margulies BJ, Clements JE. A single amino acid change and truncated TM are sufficient for simian immunodeficiency virus to enter cells using CCR5 in a CD4-independent pathway. Virology 341:12-23 (2005).
Bonavia, A., Bullock, B.T., Gisselman, K.M., Margulies, B.J., and J.E. Clements. 2005. A Single Amino Acid Change and Truncated TM are Sufficient for SIV to Enter Cells Using CCR5 in a CD4-Independent Pathway. Virology 341:12-23.
Margulies, B.J., and W. Gibson. 2007. The Chemokine Receptor Homologue Encoded by US27 of Human Cytomegalovirus is Heavily Glycosylated and Is Present in Infected Human Foreskin Fibroblasts and Enveloped Virus Particles. Virus Res.123:57-71.
Johnson, T.P,. Frey, R., Modugno, M., Brennan, T.P., and B.J. Margulies. 2007. Development of an Acyclovir Implant for the Long-Term Control of Herpes Simplex Virus Infection. Int J Antimicrob Agents 30:428-435.
Johnson, T.P. and B.J. Margulies. 2007. Long-Term Suppression of Herpesvirus Infection (provisional patent #60805381, 2006; patent pending #11/766,298, 2007)