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Development and characterization of a vaginal film containing dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), for prevention of HIV-1 sexual transmission

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Abstract

Dapivirine, a non-nucleoside reverse transcriptase inhibitor, is a potent and promising anti-HIV molecule. It is currently being investigated for use as a vaginal microbicide in two-dosage forms, a semi-solid gel and a silicone elastomer ring. Quick-dissolving films are promising and attractive dosage forms that may provide an alternative platform for the vaginal delivery of microbicide drug candidates. Vaginal films may provide advantages such as discreet use, no product leakage during use, lack of requirement for an applicator for insertion, rapid drug release, and minimal packaging and reduced wastage. Within this study, the in vitro bioactivity of dapivirine as compared with the non-nucleoside reverse transcriptase inhibitor UC781 was further established, and a quick dissolve film was developed for vaginal application of dapivirine for prevention of HIV infection. The developed film was characterized with respect to its physical and chemical attributes including water content, mechanical strength, drug release profile, permeability, compatibility with lactobacilli, and bioactivity. The anti-HIV activity of the formulated dapivirine film was confirmed in in vitro and ex vivo models. Importantly, the physical and chemical properties of the film as well as its bioactivity were maintained for a period of 18 months. In conclusion, a vaginal film containing dapivirine was developed and characterized. The film was shown to prevent HIV-1 infection in vitro and ex vivo and have acceptable characteristics which make this film a promising candidate for testing as vaginal microbicide.

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Acknowledgments

The work presented was supported through a grant from the International Partnership for Microbicides and the National Institute of Allergy and Infectious Diseases at the National Institute of Health (IPCP U19, AI082639). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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Authors and Affiliations

  1. Magee-Womens Research Institute, 204 Craft Ave, B533, Pittsburgh, PA, 15213, USA

    Ayman Akil

  2. Magee-Womens Research Institute, 204 Craft Ave, B503, Pittsburgh, PA, 15213, USA

    Charlene S. Dezzutti

  3. Magee-Womens Research Institute, 204 Craft Ave, A522, Pittsburgh, PA, 15213, USA

    Bernard J. Moncla

  4. Magee-Womens Research Institute, 204 Craft Ave, B535, Pittsburgh, PA, 15213, USA

    Marilyn R. Cost

  5. Magee-Womens Research Institute, 204 Craft Ave, B509, Pittsburgh, PA, 15213, USA

    Mingguang Li & Lisa Cencia Rohan

  6. Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA

    Ayman Akil & Lisa Cencia Rohan

  7. Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA

    Michael A. Parniak

  8. Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Charlene S. Dezzutti, Bernard J. Moncla & Lisa Cencia Rohan

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  1. Ayman Akil
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Correspondence to Lisa Cencia Rohan.

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Akil, A., Parniak, M.A., Dezzutti, C.S. et al. Development and characterization of a vaginal film containing dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), for prevention of HIV-1 sexual transmission. Drug Deliv. and Transl. Res. 1, 209–222 (2011). https://doi.org/10.1007/s13346-011-0022-6

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  • DOI: https://doi.org/10.1007/s13346-011-0022-6

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