{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:22:01Z","timestamp":1788852121704,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health\/U.S. Food and Administration","award":["1R43FD005345-01A1"],"award-info":[{"award-number":["1R43FD005345-01A1"]}]},{"name":"National Institutes of Health\/U.S. Food and Administration","award":["2R44FD005345-02"],"award-info":[{"award-number":["2R44FD005345-02"]}]},{"name":"Center for Dermal Research, Rutgers-The State University of New Jersey","award":["1R43FD005345-01A1"],"award-info":[{"award-number":["1R43FD005345-01A1"]}]},{"name":"Center for Dermal Research, Rutgers-The State University of New Jersey","award":["2R44FD005345-02"],"award-info":[{"award-number":["2R44FD005345-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Adapalene is a synthetic retinoid used as a treatment for acne vulgaris. In this study, we attempted to evaluate the dermal pharmacokinetics of adapalene utilizing experimental and in silico tools. Methods: We utilized three over the counter (OTC) adapalene gels to evaluate local dermal pharmacokinetics. A data-driven, robust, mechanistic dermal physiologically based pharmacokinetic (PBPK) model was developed by integrating the physicochemical properties of adapalene, the formulation attributes of the gels, and the biophysical aspects of dermal absorption. The dermal PBPK model was validated against experimental data using in vitro release studies and in vitro permeation studies with human cadaver skin. A clinical study was performed to evaluate the effects of adapalene from the three gel formulations. The impact of adapalene delivery from three gels on the stratum corneum (SC) thickness, pilosebaceous unit area, keratinocyte number, and epidermal thickness was captured using a non-invasive technique, line-field confocal optical coherence tomography (LC\u2013OCT). These responses were evaluated using an Emax model. Results: The dermal PBPK model has successfully predicted adapalene penetration profiles across different gel formulations. The model accuracy, in predicting drug release and permeation characteristics, was confirmed using the experimental data. Clinical evaluation revealed formulation-dependent differences in adapalene\u2019s effects on measured skin parameters, with distinct pharmacodynamic profiles observed for each gel formulation. Conclusions: The overall study gave us a detailed insight into potential effects of formulation on the dermal pharmacokinetics and pharmacodynamics of adapalene using three marketed gels.<\/jats:p>","DOI":"10.3390\/pharmaceutics17091108","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:25:57Z","timestamp":1756189557000},"page":"1108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Mechanistic Physiologically Based Pharmacokinetic\/Pharmacodynamic Modeling Approach Informed by In Vitro and Clinical Studies for Topical Administration of Adapalene Gels"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8684-2318","authenticated-orcid":false,"given":"Namrata S.","family":"Matharoo","sequence":"first","affiliation":[{"name":"Center for Dermal Research, Rutgers, The State University of New Jersey, 145 Bevier Road, Piscataway, NJ 08854, USA"},{"name":"Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Rd, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3084-1989","authenticated-orcid":false,"given":"Harsha T.","family":"Garimella","sequence":"additional","affiliation":[{"name":"CFD Research Corporation, 6820 Moquin Dr NW, Huntsville, AL 35806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6282-801X","authenticated-orcid":false,"given":"Thu M.","family":"Truong","sequence":"additional","affiliation":[{"name":"Montefiore Medical Center, Division of Dermatology, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2885-2315","authenticated-orcid":false,"given":"Saiaditya","family":"Badeti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce X.","family":"Cui","sequence":"additional","affiliation":[{"name":"Center for Dermal Research, Rutgers, The State University of New Jersey, 145 Bevier Road, Piscataway, NJ 08854, USA"},{"name":"Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Rd, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sesha Rajeswari","family":"Talluri","sequence":"additional","affiliation":[{"name":"Center for Dermal Research, Rutgers, The State University of New Jersey, 145 Bevier Road, Piscataway, NJ 08854, USA"},{"name":"Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Rd, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitkumar","family":"Virani","sequence":"additional","affiliation":[{"name":"Center for Dermal Research, Rutgers, The State University of New Jersey, 145 Bevier Road, Piscataway, NJ 08854, USA"},{"name":"Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Rd, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babar K.","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bozena","family":"Michniak-Kohn","sequence":"additional","affiliation":[{"name":"Center for Dermal Research, Rutgers, The State University of New Jersey, 145 Bevier Road, Piscataway, NJ 08854, USA"},{"name":"Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Rd, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/1523-1747.ep12676801","article-title":"An overview of acne","volume":"62","author":"Kligman","year":"1974","journal-title":"J. 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