Tenofovir vaginal film as a potential MPT product against HIV-1 and HSV-2 acquisition: formulation development and preclinical assessment in non-human primates
Tenofovir (TFV) is an adenosine nucleotide analog with activity against HIV and HSV-2. Secondary analyses of clinical trials evaluating TFV gel as pre-exposure prophylaxis (PrEP) for HIV have shown that gel formulations of TFV provide significant protection against both HIV and HSV-2 acquisition in...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Reproductive Health |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/frph.2023.1217835/full |
| _version_ | 1797745398733864960 |
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| author | Sravan Kumar Patel Sravan Kumar Patel Hrushikesh Agashe Hrushikesh Agashe Dorothy L. Patton Yvonne Sweeney May A. Beamer Craig W. Hendrix Sharon L. Hillier Sharon L. Hillier Lisa C. Rohan Lisa C. Rohan Lisa C. Rohan |
| author_facet | Sravan Kumar Patel Sravan Kumar Patel Hrushikesh Agashe Hrushikesh Agashe Dorothy L. Patton Yvonne Sweeney May A. Beamer Craig W. Hendrix Sharon L. Hillier Sharon L. Hillier Lisa C. Rohan Lisa C. Rohan Lisa C. Rohan |
| author_sort | Sravan Kumar Patel |
| collection | DOAJ |
| description | Tenofovir (TFV) is an adenosine nucleotide analog with activity against HIV and HSV-2. Secondary analyses of clinical trials evaluating TFV gel as pre-exposure prophylaxis (PrEP) for HIV have shown that gel formulations of TFV provide significant protection against both HIV and HSV-2 acquisition in women who had evidence of use. An alternate quick-dissolving polymeric thin film, to deliver TFV (20 and 40 mg) has been developed as a potential multipurpose technology (MPT) platform. Film formulation was developed based on excipient compatibility, stability, and ability to incorporate TFV doses. Placebo, low dose (20 mg), and high dose (40 mg) films were utilized in these studies. The developed film platform efficiently incorporated the high dose of TFV (40 mg/film), released more than 50% of drug in 15 min with no in vitro toxicity. Pharmacological activity was confirmed in an ex vivo HIV-1 challenge study, which showed a reduction in HIV-1 infection with TFV films. Films were stable at both doses for at least 2 years. These films were found to be safe in macaques with repeated exposure for 2 weeks as evidenced by minimal perturbation to tissues, microbiome, neutrophil influx, and pH. Macaque sized TFV film (11.2 mg) evaluated in a pigtail macaque model showed higher vaginal tissue concentrations of TFV and active TFV diphosphate compared to a 15 mg TFV loaded gel. These studies confirm that TFV films are stable, safe and efficiently deliver the drug in cervicovaginal compartments supporting their further clinical development. |
| first_indexed | 2024-03-12T15:22:45Z |
| format | Article |
| id | doaj.art-4f7fdef639424cfe93dc0365ccf457bf |
| institution | Directory Open Access Journal |
| issn | 2673-3153 |
| language | English |
| last_indexed | 2024-03-12T15:22:45Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Reproductive Health |
| spelling | doaj.art-4f7fdef639424cfe93dc0365ccf457bf2023-08-10T23:10:03ZengFrontiers Media S.A.Frontiers in Reproductive Health2673-31532023-08-01510.3389/frph.2023.12178351217835Tenofovir vaginal film as a potential MPT product against HIV-1 and HSV-2 acquisition: formulation development and preclinical assessment in non-human primatesSravan Kumar Patel0Sravan Kumar Patel1Hrushikesh Agashe2Hrushikesh Agashe3Dorothy L. Patton4Yvonne Sweeney5May A. Beamer6Craig W. Hendrix7Sharon L. Hillier8Sharon L. Hillier9Lisa C. Rohan10Lisa C. Rohan11Lisa C. Rohan12Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, United StatesMagee-Womens Research Institute, Pittsburgh, PA, United StatesDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, United StatesMagee-Womens Research Institute, Pittsburgh, PA, United StatesDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, United StatesDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, United StatesMagee-Womens Research Institute, Pittsburgh, PA, United StatesDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesMagee-Womens Research Institute, Pittsburgh, PA, United StatesDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, PA, United StatesDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, United StatesMagee-Womens Research Institute, Pittsburgh, PA, United StatesDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, PA, United StatesTenofovir (TFV) is an adenosine nucleotide analog with activity against HIV and HSV-2. Secondary analyses of clinical trials evaluating TFV gel as pre-exposure prophylaxis (PrEP) for HIV have shown that gel formulations of TFV provide significant protection against both HIV and HSV-2 acquisition in women who had evidence of use. An alternate quick-dissolving polymeric thin film, to deliver TFV (20 and 40 mg) has been developed as a potential multipurpose technology (MPT) platform. Film formulation was developed based on excipient compatibility, stability, and ability to incorporate TFV doses. Placebo, low dose (20 mg), and high dose (40 mg) films were utilized in these studies. The developed film platform efficiently incorporated the high dose of TFV (40 mg/film), released more than 50% of drug in 15 min with no in vitro toxicity. Pharmacological activity was confirmed in an ex vivo HIV-1 challenge study, which showed a reduction in HIV-1 infection with TFV films. Films were stable at both doses for at least 2 years. These films were found to be safe in macaques with repeated exposure for 2 weeks as evidenced by minimal perturbation to tissues, microbiome, neutrophil influx, and pH. Macaque sized TFV film (11.2 mg) evaluated in a pigtail macaque model showed higher vaginal tissue concentrations of TFV and active TFV diphosphate compared to a 15 mg TFV loaded gel. These studies confirm that TFV films are stable, safe and efficiently deliver the drug in cervicovaginal compartments supporting their further clinical development.https://www.frontiersin.org/articles/10.3389/frph.2023.1217835/fullHIV preventiongenital herpesmultipurpose technologytenofovirvaginal filmwomen health |
| spellingShingle | Sravan Kumar Patel Sravan Kumar Patel Hrushikesh Agashe Hrushikesh Agashe Dorothy L. Patton Yvonne Sweeney May A. Beamer Craig W. Hendrix Sharon L. Hillier Sharon L. Hillier Lisa C. Rohan Lisa C. Rohan Lisa C. Rohan Tenofovir vaginal film as a potential MPT product against HIV-1 and HSV-2 acquisition: formulation development and preclinical assessment in non-human primates Frontiers in Reproductive Health HIV prevention genital herpes multipurpose technology tenofovir vaginal film women health |
| title | Tenofovir vaginal film as a potential MPT product against HIV-1 and HSV-2 acquisition: formulation development and preclinical assessment in non-human primates |
| title_full | Tenofovir vaginal film as a potential MPT product against HIV-1 and HSV-2 acquisition: formulation development and preclinical assessment in non-human primates |
| title_fullStr | Tenofovir vaginal film as a potential MPT product against HIV-1 and HSV-2 acquisition: formulation development and preclinical assessment in non-human primates |
| title_full_unstemmed | Tenofovir vaginal film as a potential MPT product against HIV-1 and HSV-2 acquisition: formulation development and preclinical assessment in non-human primates |
| title_short | Tenofovir vaginal film as a potential MPT product against HIV-1 and HSV-2 acquisition: formulation development and preclinical assessment in non-human primates |
| title_sort | tenofovir vaginal film as a potential mpt product against hiv 1 and hsv 2 acquisition formulation development and preclinical assessment in non human primates |
| topic | HIV prevention genital herpes multipurpose technology tenofovir vaginal film women health |
| url | https://www.frontiersin.org/articles/10.3389/frph.2023.1217835/full |
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