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. Semenkow, Nicole M. Johnson, David J Maggs, Barry J. Margulies

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Article number34
JournalVirology Journal
Volume11
Issue number1
DOIs
StatePublished - Feb 22 2014

Fingerprint

Herpesviridae Infections
Felidae
Silicones
Polymers
Pharmacokinetics
Equipment and Supplies
Cats
Pharmaceutical Preparations
Herpesviridae
Placebos
Virus Shedding
Conjunctivitis
Acyclovir
Compliance
Oral Administration
penciclovir
Cell Culture Techniques

Keywords

  • Controlled release
  • Feline herpesvirus
  • Herpetic disease
  • Implant
  • Ocular
  • Penciclovir
  • Silicone

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

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. / Semenkow, Samantha L.; Johnson, Nicole M.; Maggs, David J; Margulies, Barry J.

In: Virology Journal, Vol. 11, No. 1, 34, 22.02.2014.

Research output: Contribution to journalArticle

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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.",
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