Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc
| Autor: | Claire J. Forbes, R. Karl Malcolm, Leslie Geer, Laura A. Doyle, Per Johan Klasse, A. David Woolfson, Robin J. Shattock, Laurie Goldman, Ronald S. Veazey, John P. Moore, Brendan C.O. Muldoon, Mark Mitchnick, Deborah Lowry |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Pharmaceutical Science
HIV Infections Pharmacology Article Maraviroc chemistry.chemical_compound Silicone Cyclohexanes HIV Fusion Inhibitors medicine Animals Humans Vaginal delivery Vaginal microbicide Triazoles Silicone Gels Macaca mulatta Microbicides for sexually transmitted diseases Administration Intravaginal medicine.anatomical_structure chemistry Delayed-Action Preparations Drug delivery Immunology Vagina HIV-1 Silicone Elastomers Vaginal Creams Foams and Jellies Female Gels |
| ISSN: | 1873-4995 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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