{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:21:45Z","timestamp":1790014905163,"version":"4.0.1"},"reference-count":33,"publisher":"American Chemical Society (ACS)","issue":"5","license":[{"start":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T00:00:00Z","timestamp":1427932800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["IPCP U19, AI082639"],"award-info":[{"award-number":["IPCP U19, AI082639"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 \u03bcg\/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.<\/jats:p>","DOI":"10.1021\/mp4007024","type":"journal-article","created":{"date-parts":[[2014,4,2]],"date-time":"2014-04-02T18:21:44Z","timestamp":1396462904000},"page":"1533-1541","source":"Crossref","is-referenced-by-count":33,"title":["Increased Dapivirine Tissue Accumulation through Vaginal\nFilm Codelivery of Dapivirine and Tenofovir"],"prefix":"10.1021","volume":"11","author":[{"given":"Ayman","family":"Akil","sequence":"first","affiliation":[{"name":"Magee-Womens Research Institute , , ,","place":["Pittsburgh, Pennsylvania, United States, 15213"]},{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brid","family":"Devlin","sequence":"additional","affiliation":[{"name":"International Partnership for Microbicides , Silver Spring , ,","place":["Maryland, United States, 20910"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Cost","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute , , ,","place":["Pittsburgh, Pennsylvania, United States, 15213"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Cencia","family":"Rohan","sequence":"additional","affiliation":[{"name":"Magee-Womens Research Institute , , ,","place":["Pittsburgh, Pennsylvania, United States, 15213"]},{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]},{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,4,2]]},"reference":[{"key":"2026090221442590500_cit1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/jac\/dki464","article-title":"Dawn of non-nucleoside inhibitor-based anti-HIV microbicides","volume":"57","author":"D\u2019Cruz","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"2026090221442590500_cit2","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1128\/AAC.01156-08","article-title":"Inhibition of human\nimmunodeficiency virus type 1 infection by the candidate microbicide\ndapivirine, a nonnucleoside reverse transcriptase inhibitor","volume":"53","author":"Fletcher","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090221442590500_cit3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2174\/157016212799304643","article-title":"Reverse transcriptase inhibitors as microbicides","volume":"10","author":"Lewi","year":"2012","journal-title":"Curr. HIV Res."},{"key":"2026090221442590500_cit4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.bpobgyn.2012.02.001","article-title":"Future strategies in microbicide development","volume":"26","author":"Rosenberg","year":"2012","journal-title":"Best Pract. Res., Clin. Obstet. Gynaecol."},{"key":"2026090221442590500_cit5","doi-asserted-by":"crossref","first-page":"a007385","DOI":"10.1101\/cshperspect.a007385","article-title":"Microbicides: topical prevention against HIV","volume":"2","author":"Shattock","year":"2012","journal-title":"Cold Spring Harbor Perspect. Med."},{"key":"2026090221442590500_cit6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1177\/095632020901900401","article-title":"The future of HIV microbicides: challenges\nand opportunities","volume":"19","author":"Garg","year":"2009","journal-title":"Antiviral Chem. Chemother."},{"key":"2026090221442590500_cit7","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1128\/AAC.49.5.1830-1836.2005","article-title":"Combination of candidate microbicides\ncellulose acetate 1,2-benzenedicarboxylate and UC781 has synergistic\nand complementary effects against human immunodeficiency virus type\n1 infection","volume":"49","author":"Liu","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090221442590500_cit8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/01.olq.0000223287.46097.4b","article-title":"Carrageenan\/MIV-150\n(PC-815), a combination microbicide","volume":"34","author":"Fernandez-Romero","year":"2007","journal-title":"Sex. Transm.\nDis."},{"key":"2026090221442590500_cit9","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.fertnstert.2007.01.131","article-title":"Mucosal safety of PHI-443 and stampidine as a combination\nmicrobicide to prevent genital transmission of HIV-1","volume":"88","author":"D\u2019Cruz","year":"2007","journal-title":"Fertil. Steril."},{"key":"2026090221442590500_cit10","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.antiviral.2007.03.004","article-title":"Synergistic inhibition of HIV-1 infection\nby combinations of soluble polyanions with other potential microbicides","volume":"75","author":"Gantlett","year":"2007","journal-title":"Antiviral Res."},{"key":"2026090221442590500_cit11","doi-asserted-by":"crossref","first-page":"10358","DOI":"10.1128\/JVI.01073-09","article-title":"Complete protection\nfrom repeated vaginal simian-human immunodeficiency virus exposures\nin macaques by a topical gel containing tenofovir alone or with emtricitabine","volume":"83","author":"Parikh","year":"2009","journal-title":"J. Virol."},{"key":"2026090221442590500_cit12","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1002\/jps.23089","article-title":"Design of tenofovir-UC781 combination microbicide vaginal\ngels","volume":"101","author":"Kiser","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"2026090221442590500_cit13","doi-asserted-by":"crossref","first-page":"e15835","DOI":"10.1371\/journal.pone.0015835","article-title":"An antiretroviral\/zinc combination\ngel provides 24 h of complete protection against vaginal SHIV infection\nin macaques","volume":"6","author":"Kenney","year":"2011","journal-title":"PLoS One"},{"key":"2026090221442590500_cit14","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.antiviral.2012.08.004","article-title":"Safety and efficacy\nof tenofovir\/IQP-0528 combination gels - a dual compartment microbicide\nfor HIV-1 prevention","volume":"96","author":"Dezzutti","year":"2012","journal-title":"Antiviral Res."},{"key":"2026090221442590500_cit15","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ejps.2009.11.007","article-title":"Segmented\npolyurethane intravaginal rings for the sustained combined delivery\nof antiretroviral agents dapivirine and tenofovir","volume":"39","author":"Johnson","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"2026090221442590500_cit16","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.ejps.2012.12.002","article-title":"A silicone elastomer vaginal ring\nfor HIV prevention containing two microbicides with different mechanisms\nof action","volume":"48","author":"Fetherston","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"2026090221442590500_cit17","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1097\/QAD.0b013e3283491f89","article-title":"Synergy\nagainst drug-resistant HIV-1 with the microbicide antiretrovirals,\ndapivirine and tenofovir, in combination","volume":"25","author":"Schader","year":"2011","journal-title":"AIDS"},{"key":"2026090221442590500_cit18","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1128\/AAC.05821-11","article-title":"In vitro resistance profile of the candidate HIV-1\nmicrobicide drug dapivirine","volume":"56","author":"Schader","year":"2012","journal-title":"Antimicrob. Agents\nChemother."},{"key":"2026090221442590500_cit19","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1365-2796.2011.02454.x","article-title":"Specific microbicides in the prevention of HIV infection","volume":"270","author":"Kelly","year":"2011","journal-title":"J. Intern. Med."},{"key":"2026090221442590500_cit20","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1146\/annurev.pharmtox.48.113006.094906","article-title":"Topical microbicides to prevent HIV:\nclinical drug development challenges","volume":"49","author":"Hendrix","year":"2009","journal-title":"Annu.\nRev. Pharmacol. Toxicol."},{"key":"2026090221442590500_cit21","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.antiviral.2012.09.011","article-title":"In vitro profiling of the vaginal\npermeation potential of anti-HIV microbicides and the influence of\nformulation excipients","volume":"96","author":"Grammen","year":"2012","journal-title":"Antiviral Res."},{"key":"2026090221442590500_cit22","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1021\/mp4002365","article-title":"In Vitro and Ex Vivo Evaluation of Polymeric Nanoparticles\nfor Vaginal and Rectal Delivery of the Anti-HIV Drug Dapivirine","volume":"10","author":"das Neves","year":"2013","journal-title":"Mol. Pharmaceutics"},{"key":"2026090221442590500_cit23","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1089\/aid.2008.0184","article-title":"Safety and\navailability of dapivirine (TMC120) delivered from an intravaginal\nring","volume":"25","author":"Romano","year":"2009","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"2026090221442590500_cit24","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1097\/QAI.0b013e3181acb536","article-title":"Safety and pharmacokinetics of dapivirine\ndelivery from matrix and reservoir intravaginal rings to HIV-negative\nwomen","volume":"51","author":"Nel","year":"2009","journal-title":"J. Acquired Immune Defic. Syndr."},{"key":"2026090221442590500_cit25","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1097\/QAD.0b013e32832c413d","article-title":"Safety, tolerability,\nand systemic absorption of dapivirine vaginal microbicide gel in healthy,\nHIV-negative women","volume":"23","author":"Nel","year":"2009","journal-title":"AIDS"},{"key":"2026090221442590500_cit26","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/QAI.0b013e3181e3293a","article-title":"Pharmacokinetics\nof 2 dapivirine vaginal microbicide gels and their safety vs. Hydroxyethyl\ncellulose-based universal placebo gel","volume":"55","author":"Nel","year":"2010","journal-title":"J. Acquired\nImmune Defic. Syndr."},{"key":"2026090221442590500_cit27","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1089\/aid.2009.0227","article-title":"Pharmacokinetic assessment of dapivirine\nvaginal microbicide gel in healthy, HIV-negative women","volume":"26","author":"Nel","year":"2010","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"2026090221442590500_cit28","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s13346-011-0022-6","article-title":"Development and characterization of a vaginal film\ncontaining dapivirine, a non-nucleoside reverse transcriptase inhibitor\n(NNRTI), for prevention of HIV-1 sexual transmission","volume":"1","author":"Akil","year":"2011","journal-title":"Drug Delivery Transl. Res."},{"key":"2026090221442590500_cit29","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0010-7824(99)00010-4","article-title":"A vaginal fluid simulant","volume":"59","author":"Owen","year":"1999","journal-title":"Contraception"},{"key":"2026090221442590500_cit30","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.bpobgyn.2012.01.004","article-title":"Formulation, pharmacokinetics and pharmacodynamics\nof topical microbicides","volume":"26","author":"Adams","year":"2012","journal-title":"Best Pract. Res., Clin.\nObstet. Gynaecol."},{"key":"2026090221442590500_cit31","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1097\/COH.0b013e328305b96e","article-title":"Microbicide\ndelivery: formulation technologies and strategies","volume":"3","author":"Romano","year":"2008","journal-title":"Curr. Opin. HIV AIDS"},{"key":"2026090221442590500_cit32","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1046\/j.1365-2567.1999.00675.x","article-title":"Distribution of lymphocytes\nand adhesion molecules in human cervix and vagina","volume":"96","author":"Johansson","year":"1999","journal-title":"Immunology"},{"key":"2026090221442590500_cit33","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/AAC.48.1.337-339.2004","article-title":"In vitro evaluation of nonnucleoside reverse transcriptase\ninhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus\nmicrobicides","volume":"48","author":"Van Herrewege","year":"2004","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Molecular Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/mp4007024","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article-pdf\/11\/5\/1533\/14372019\/mp4007024.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article-pdf\/11\/5\/1533\/14372019\/mp4007024.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:48:43Z","timestamp":1788400123000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article\/11\/5\/1533\/1379545\/Increased-Dapivirine-Tissue-Accumulation-through"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,2]]},"references-count":33,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2014,4,2]]},"published-print":{"date-parts":[[2014,5,5]]}},"URL":"https:\/\/doi.org\/10.1021\/mp4007024","relation":{},"ISSN":["1543-8384","1543-8392"],"issn-type":[{"value":"1543-8384","type":"print"},{"value":"1543-8392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,2]]}}}