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Increased Dapivirine Tissue Accumulation through Vaginal Film Codelivery of Dapivirine and Tenofovir

[Image: see text] The HIV-1 replication inhibitor dapivirine (DPV) is one of the most promising drug candidates being used in topical microbicide products for prevention of HIV-1 sexual transmission. To be able to block HIV-1 replication, DPV must have access to the viral reverse transcriptase enzym...

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Autores principales: Akil, Ayman, Devlin, Brid, Cost, Marilyn, Rohan, Lisa Cencia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018102/
https://www.ncbi.nlm.nih.gov/pubmed/24693866
http://dx.doi.org/10.1021/mp4007024
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author Akil, Ayman
Devlin, Brid
Cost, Marilyn
Rohan, Lisa Cencia
author_facet Akil, Ayman
Devlin, Brid
Cost, Marilyn
Rohan, Lisa Cencia
author_sort Akil, Ayman
collection PubMed
description [Image: see text] The HIV-1 replication inhibitor dapivirine (DPV) is one of the most promising drug candidates being used in topical microbicide products for prevention of HIV-1 sexual transmission. To be able to block HIV-1 replication, DPV must have access to the viral reverse transcriptase enzyme. The window for DPV to access the enzyme happens during the HIV-1 cellular infection cycle. Thus, in order for DPV to exert its anti-HIV activity, it must be present in the mucosal tissue or cells where HIV-1 infection occurs. A dosage form containing DPV must be able to deliver the drug to the tissue site of action. Polymeric films are solid dosage forms that dissolve and release their payload upon contact with fluids. Films have been used as vaginal delivery systems of topical microbicide drug candidates including DPV. For use in topical microbicide products containing DPV, polymeric films must prove their ability to deliver DPV to the target tissue site of action. Ex vivo exposure studies of human ectocervical tissue to DPV film revealed that DPV was released from the film and did diffuse into the tissue in a concentration dependent manner indicating a process of passive diffusion. Analysis of drug distribution in the tissue revealed that DPV accumulated mostly at the basal layer of the epithelium infiltrating the upper part of the stroma. Furthermore, as a combination microbicide product, codelivery of DPV and TFV from a polymeric film resulted in a significant increase in DPV tissue concentration [14.21 (single entity film) and 31.03 μg/g (combination film)], whereas no impact on TFV tissue concentration was found. In vitro release experiments showed that this observation was due to a more rapid DPV release from the combination film as compared to the single entity film. In conclusion, the findings of this study confirm the ability of polymeric films to deliver DPV and TFV to human ectocervical tissue and show that codelivery of the two agents has a significant impact on DPV tissue accumulation. These findings support the use of polymeric films for topical microbicide products containing DPV and/or TFV.
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spelling pubmed-40181022015-04-02 Increased Dapivirine Tissue Accumulation through Vaginal Film Codelivery of Dapivirine and Tenofovir Akil, Ayman Devlin, Brid Cost, Marilyn Rohan, Lisa Cencia Mol Pharm [Image: see text] The HIV-1 replication inhibitor dapivirine (DPV) is one of the most promising drug candidates being used in topical microbicide products for prevention of HIV-1 sexual transmission. To be able to block HIV-1 replication, DPV must have access to the viral reverse transcriptase enzyme. The window for DPV to access the enzyme happens during the HIV-1 cellular infection cycle. Thus, in order for DPV to exert its anti-HIV activity, it must be present in the mucosal tissue or cells where HIV-1 infection occurs. A dosage form containing DPV must be able to deliver the drug to the tissue site of action. Polymeric films are solid dosage forms that dissolve and release their payload upon contact with fluids. Films have been used as vaginal delivery systems of topical microbicide drug candidates including DPV. For use in topical microbicide products containing DPV, polymeric films must prove their ability to deliver DPV to the target tissue site of action. Ex vivo exposure studies of human ectocervical tissue to DPV film revealed that DPV was released from the film and did diffuse into the tissue in a concentration dependent manner indicating a process of passive diffusion. Analysis of drug distribution in the tissue revealed that DPV accumulated mostly at the basal layer of the epithelium infiltrating the upper part of the stroma. Furthermore, as a combination microbicide product, codelivery of DPV and TFV from a polymeric film resulted in a significant increase in DPV tissue concentration [14.21 (single entity film) and 31.03 μg/g (combination film)], whereas no impact on TFV tissue concentration was found. In vitro release experiments showed that this observation was due to a more rapid DPV release from the combination film as compared to the single entity film. In conclusion, the findings of this study confirm the ability of polymeric films to deliver DPV and TFV to human ectocervical tissue and show that codelivery of the two agents has a significant impact on DPV tissue accumulation. These findings support the use of polymeric films for topical microbicide products containing DPV and/or TFV. American Chemical Society 2014-04-02 2014-05-05 /pmc/articles/PMC4018102/ /pubmed/24693866 http://dx.doi.org/10.1021/mp4007024 Text en Copyright © 2014 American Chemical Society
spellingShingle Akil, Ayman
Devlin, Brid
Cost, Marilyn
Rohan, Lisa Cencia
Increased Dapivirine Tissue Accumulation through Vaginal Film Codelivery of Dapivirine and Tenofovir
title Increased Dapivirine Tissue Accumulation through Vaginal Film Codelivery of Dapivirine and Tenofovir
title_full Increased Dapivirine Tissue Accumulation through Vaginal Film Codelivery of Dapivirine and Tenofovir
title_fullStr Increased Dapivirine Tissue Accumulation through Vaginal Film Codelivery of Dapivirine and Tenofovir
title_full_unstemmed Increased Dapivirine Tissue Accumulation through Vaginal Film Codelivery of Dapivirine and Tenofovir
title_short Increased Dapivirine Tissue Accumulation through Vaginal Film Codelivery of Dapivirine and Tenofovir
title_sort increased dapivirine tissue accumulation through vaginal film codelivery of dapivirine and tenofovir
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018102/
https://www.ncbi.nlm.nih.gov/pubmed/24693866
http://dx.doi.org/10.1021/mp4007024
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