Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Claire J. Forbes, Deborah Lowry, Leslie Geer, Ronald S. Veazey, Robin J. Shattock, Per J. Klasse, Mark Mitchnick, Laurie Goldman, Lara A Doyle, Brendan C.O. Muldoon, A. David Woolfson, John P. Moore, R. Karl Malcolm

Research output: Contribution to journalArticle

Abstract

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.
Original languageEnglish
Pages (from-to)161-169
Number of pages9
JournalJournal of Controlled Release
Volume156
Issue number2
Early online date12 Aug 2011
DOIs
Publication statusPublished - 10 Dec 2011

Bibliographical note

© 2011, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • intravaginal administration
  • animals
  • cyclohexanes
  • delayed-action preparations
  • female
  • gels
  • HIV fusion inhibitors
  • HIV infections
  • HIV-1
  • humans
  • macaca mulatta
  • silicone elastomers
  • triazoles
  • vagina
  • vaginal creams
  • foams
  • jellies

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  • Cite this

    Forbes, C. J., Lowry, D., Geer, L., Veazey, R. S., Shattock, R. J., Klasse, P. J., Mitchnick, M., Goldman, L., Doyle, L. A., Muldoon, B. C. O., Woolfson, A. D., Moore, J. P., & Malcolm, R. K. (2011). Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc. Journal of Controlled Release, 156(2), 161-169. https://doi.org/10.1016/j.jconrel.2011.08.006