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

TitleNon-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc.
Publication TypeJournal Article
Year of Publication2011
AuthorsForbes CJ, Lowry D, Geer L, Veazey RS, Shattock RJ, Klasse PJohan, Mitchnick M, Goldman L, Doyle LA, Muldoon BCO, A Woolfson D, Moore JP, R Malcolm K
JournalJ Control Release
Date Published2011 Dec 10
KeywordsAdministration, Intravaginal, Animals, Cyclohexanes, Delayed-Action Preparations, Female, Gels, HIV Fusion Inhibitors, HIV Infections, HIV-1, Humans, Macaca mulatta, Silicone Elastomers, Triazoles, Vagina, Vaginal Creams, Foams, and Jellies

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.

Alternate JournalJ Control Release
PubMed ID21864598
PubMed Central IDPMC3220778
Grant ListU19 AI076982 / AI / NIAID NIH HHS / United States
U19 AI076982-01 / AI / NIAID NIH HHS / United States
U19 AI76982 / AI / NIAID NIH HHS / United States

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