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Antiviral Agents

Electrospun Solid Dispersions of Maraviroc for Rapid Intravaginal Preexposure Prophylaxis of HIV

Cameron Ball, Kim A. Woodrow
Cameron Ball
University of Washington, Seattle, Washington, USA
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Kim A. Woodrow
University of Washington, Seattle, Washington, USA
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DOI: 10.1128/AAC.02564-14
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ABSTRACT

The development of topical anti-human immunodeficiency virus (HIV) microbicides may provide women with strategies to protect themselves against sexual HIV transmission. Pericoital drug delivery systems intended for use immediately before sex, such as microbicide gels, must deliver high drug doses for maximal effectiveness. The goal of achieving a high antiretroviral dose is complicated by the need to simultaneously retain the dose and quickly release drug compounds into the tissue. For drugs with limited solubility in vaginal gels, increasing the gel volume to increase the dose can result in leakage. While solid dosage forms like films and tablets increase retention, they often require more than 15 min to fully dissolve, potentially increasing the risk of inducing epithelial abrasions during sex. Here, we demonstrate that water-soluble electrospun fibers, with their high surface area-to-volume ratio and ability to disperse antiretrovirals, can serve as an alternative solid dosage form for microbicides requiring both high drug loading and rapid hydration. We formulated maraviroc at up to 28 wt% into electrospun solid dispersions made from either polyvinylpyrrolidone or poly(ethylene oxide) nanofibers or microfibers and investigated the role of drug loading, distribution, and crystallinity in determining drug release rates into aqueous media. We show here that water-soluble electrospun materials can rapidly release maraviroc upon contact with moisture and that drug delivery is faster (less than 6 min under sink conditions) when maraviroc is electrospun in polyvinylpyrrolidone fibers containing an excipient wetting agent. These materials offer an alternative dosage form to current pericoital microbicides.

FOOTNOTES

    • Received 18 February 2014.
    • Returned for modification 31 March 2014.
    • Accepted 4 June 2014.
    • Accepted manuscript posted online 9 June 2014.
  • Supplemental material for this article may be found at http://dx.doi.org/10.1128/AAC.02564-14.

  • Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Electrospun Solid Dispersions of Maraviroc for Rapid Intravaginal Preexposure Prophylaxis of HIV
Cameron Ball, Kim A. Woodrow
Antimicrobial Agents and Chemotherapy Jul 2014, 58 (8) 4855-4865; DOI: 10.1128/AAC.02564-14

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Electrospun Solid Dispersions of Maraviroc for Rapid Intravaginal Preexposure Prophylaxis of HIV
Cameron Ball, Kim A. Woodrow
Antimicrobial Agents and Chemotherapy Jul 2014, 58 (8) 4855-4865; DOI: 10.1128/AAC.02564-14
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