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

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.

Publication DOI: https://doi.org/10.1016/j.jconrel.2011.08.006
Divisions: Life & Health Sciences
Life & Health Sciences > Pharmacy
Life & Health Sciences > Chronic and Communicable Conditions
Additional Information: © 2011, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled 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,Pharmaceutical Science
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2011-12-10
Authors: Forbes, Claire J.
Lowry, Deborah
Geer, Leslie
Veazey, Ronald S.
Shattock, Robin J.
Klasse, Per J.
Mitchnick, Mark
Goldman, Laurie
Doyle, Lara A
Muldoon, Brendan C.O.
Woolfson, A. David
Moore, John P.
Malcolm, R. Karl

Download

[img]

Version: Accepted Version

Access Restriction: Restricted to Repository staff only

License: Creative Commons Attribution Non-commercial No Derivatives


Export / Share Citation


Statistics

Additional statistics for this record