Modified Silicone Elastomer Vaginal Gels for Sustained Release of Antiretroviral HIV Microbicides

Claire J. Forbes, Clare F. McCoy, Diarmaid J. Murphy, A. David Woolfson, John P. Moore, Abbey Evans, Robin J Shattock, R. Karl Malcolm

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
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Abstract

We previously reported nonaqueous silicone elastomer gels (SEGs) for sustained vaginal administration of the CCR5-targeted entry inhibitor maraviroc (MVC). Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic cyclomethicone component was partially replaced with relatively hydrophilic silanol-terminated polydimethylsiloxanes (st-PDMS). MVC and emtricitabine (a nucleoside reverse transcriptase inhibitor), both currently under evaluation as topical microbicides to counter sexual transmission of human immunodeficiency virus type 1 (HIV-1), were used as model antiretroviral (ARV) drugs. Gel viscosity and in vitro ARV release were significantly influenced by st-PDMS molecular weight and concentration in the h-SEGs. Unexpectedly, gels prepared with lower molecular weight grades of st-PDMS showed higher viscosities. h-SEGs provided enhanced release over 24 h compared with aqueous hydroxyethylcellulose (HEC) gels, did not modify the pH of simulated vaginal fluid (SVF), and were shown to less cytotoxic than standard HEC vaginal gel. ARV solubility increased as st-PDMS molecular weight decreased (i.e., as percentage hydroxyl content increased), helping to explain the in vitro release trends. Dye ingression and SVF dilution studies confirmed the increased hydrophilicity of the h-SEGs. h-SEGs have potential for use in vaginal drug delivery, particularly for ARV-based HIV-1 microbicides.
Original languageEnglish
Pages (from-to)1422-1432
Number of pages11
JournalJournal of Pharmaceutical Sciences
Volume103
Issue number5
Early online date01 Mar 2014
DOIs
Publication statusPublished - May 2014

Keywords

  • Keywords: gels;antiinfectives;silicone elastomer;HIVmicrobicides;sustained release;HIV/AIDS;rheology;viscosity;formulation;drug delivery systems

ASJC Scopus subject areas

  • Pharmaceutical Science

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