{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:42:06Z","timestamp":1787740926297,"version":"build-2784847793"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of Taiwan","award":["MOST-110-2314-B-281-009"],"award-info":[{"award-number":["MOST-110-2314-B-281-009"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["MOST-111-2314-B-281-012"],"award-info":[{"award-number":["MOST-111-2314-B-281-012"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["CGH-MR-A110014"],"award-info":[{"award-number":["CGH-MR-A110014"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["CGH-MR-A111016"],"award-info":[{"award-number":["CGH-MR-A111016"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["CGH-MR-A111018"],"award-info":[{"award-number":["CGH-MR-A111018"]}]},{"DOI":"10.13039\/501100002811","name":"Cathay General Hospital","doi-asserted-by":"publisher","award":["MOST-110-2314-B-281-009"],"award-info":[{"award-number":["MOST-110-2314-B-281-009"]}],"id":[{"id":"10.13039\/501100002811","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002811","name":"Cathay General Hospital","doi-asserted-by":"publisher","award":["MOST-111-2314-B-281-012"],"award-info":[{"award-number":["MOST-111-2314-B-281-012"]}],"id":[{"id":"10.13039\/501100002811","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002811","name":"Cathay General Hospital","doi-asserted-by":"publisher","award":["CGH-MR-A110014"],"award-info":[{"award-number":["CGH-MR-A110014"]}],"id":[{"id":"10.13039\/501100002811","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002811","name":"Cathay General Hospital","doi-asserted-by":"publisher","award":["CGH-MR-A111016"],"award-info":[{"award-number":["CGH-MR-A111016"]}],"id":[{"id":"10.13039\/501100002811","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002811","name":"Cathay General Hospital","doi-asserted-by":"publisher","award":["CGH-MR-A111018"],"award-info":[{"award-number":["CGH-MR-A111018"]}],"id":[{"id":"10.13039\/501100002811","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>(1) Background: Human keratinocytes and murine skin express various cytochrome P450 enzymes. These include cytochrome P450 3A4, which may participate in the metabolism of cytochrome P450 3A4 substrate drugs. Desoximetasone, a topical corticosteroid and cytochrome P450 3A4 substrate, is used to treat skin conditions such as skin allergies, atopic dermatitis, and psoriasis. In this study, we aimed to investigate the anti-psoriatic effect of a low dose of desoximetasone by inhibiting cytochrome P450 3A4 metabolism in the epidermis. (2) Methods: Psoriasis-like skin was induced in BALB\/c mice via the topical administration of imiquimod. The mice were then topically treated with 0.01\u20130.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient microemulsion, 0.25% commercial desoximetasone ointment, or 0.5 mg\/gm clobetasol ointment. (3) Results: The topical application of 0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation restored the imiquimod-induced skin barrier disruption and resulted in fewer severe clinical and pathological features compared with the treatments with 0.25% commercial desoximetasone ointment and 0.5 mg\/gm clobetasol ointment. (4) Conclusions: The cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation improved and prolonged the therapeutic effect of cytochrome P450 3A4 substrate drugs and may be a promising approach for psoriasis treatment.<\/jats:p>","DOI":"10.3390\/pharmaceutics15082016","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T01:03:25Z","timestamp":1690333405000},"page":"2016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Promising Approach to Treat Psoriasis: Inhibiting Cytochrome P450 3A4 Metabolism to Enhance Desoximetasone Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6337-4817","authenticated-orcid":false,"given":"Jiun-Wen","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0578-6682","authenticated-orcid":false,"given":"Yu-Pin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Cathay General Hospital, Taipei 10630, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0051-1890","authenticated-orcid":false,"given":"Cherng-Jyr","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Cathay General Hospital, Taipei 10630, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3996-8452","authenticated-orcid":false,"given":"Chih-Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 22174, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6737-6297","authenticated-orcid":false,"given":"Shiou-Hwa","family":"Jee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, College of Medicine, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1080\/00498254.2019.1648911","article-title":"Cytochrome P450: Genotype to phenotype","volume":"50","author":"Waring","year":"2020","journal-title":"Xenobiotica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1046\/j.1523-1747.2001.01298.x","article-title":"Expression of multiple cytochrome p450 enzymes and multidrug resistance-associated transport proteins in human skin keratinocytes","volume":"116","author":"Baron","year":"2001","journal-title":"J. Investig. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0006-291X(02)02134-4","article-title":"Expression of P450 enzymes in rat whole skin and cultured epidermal keratinocytes","volume":"297","author":"Zhu","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1159\/000057751","article-title":"mRNA expression of multiple cytochrome p450 isozymes in four types of cultured skin cells","volume":"127","author":"Saeki","year":"2002","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1124\/jpet.106.105858","article-title":"Enzyme-mediated protein haptenation of dapsone and sulfamethoxazole in human keratinocytes: I. Expression and role of cytochromes P450","volume":"319","author":"Vyas","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1124\/jpet.106.111724","article-title":"Differentiation-specific factors modulate epidermal CYP1-4 gene expression in human skin in response to retinoic acid and classic aryl hydrocarbon receptor ligands","volume":"319","author":"Du","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/S0006-2952(01)00718-3","article-title":"Quantification and cellular localization of expression in human skin of genes encoding flavin-containing monooxygenases and cytochromes P450","volume":"62","author":"Janmohamed","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1159\/000131082","article-title":"Activity of different desoximetasone preparations compared to other topical corticosteroids in the vasoconstriction assay","volume":"21","author":"Borelli","year":"2008","journal-title":"Skin. Pharmacol. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Patel, R., Barker, J., and ElShaer, A. (2020). Pharmaceutical Excipients and Drug Metabolism: A Mini-Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218224"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/bdd.383","article-title":"In vitro investigation on the impact of the surface-active excipients Cremophor EL, Tween 80 and Solutol HS 15 on the metabolism of midazolam","volume":"25","author":"Huwyler","year":"2004","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0378-5173(00)00586-X","article-title":"Potential inhibitory effects of formulation ingredients on intestinal cytochrome P450","volume":"211","author":"Mountfield","year":"2000","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ejps.2008.11.002","article-title":"Nonionic surfactants are strong inhibitors of cytochrome P450 3A biotransformation activity in vitro and in vivo","volume":"36","author":"Ren","year":"2009","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1007\/s11596-010-0543-0","article-title":"Inhibitive effect of cremophor RH40 or tween 80-based self-microemulsiflying drug delivery system on cytochrome P450 3A enzymes in murine hepatocytes","volume":"30","author":"Rao","year":"2010","journal-title":"J. Huazhong Univ. Sci. Technol. Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.ejps.2013.08.016","article-title":"Enhanced intestinal absorption of etoposide by self-microemulsifying drug delivery systems: Roles of P-glycoprotein and cytochrome P450 3A inhibition","volume":"50","author":"Zhao","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kwon, M., Lim, D.Y., Lee, C.H., Jeon, J.H., Choi, M.K., and Song, I.S. (2020). Enhanced Intestinal Absorption and Pharmacokinetic Modulation of Berberine and Its Metabolites through the Inhibition of P-Glycoprotein and Intestinal Metabolism in Rats Using a Berberine Mixed Micelle Formulation. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12090882"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Guo, J.W., Chien, C.C., and Chen, J.H. (2020). CYP3A Excipient-Based Microemulsion Prolongs the Effect of Magnolol on Ischemia Stroke Rats. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080737"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chen, L.C., Cheng, Y.P., Liu, C.Y., and Guo, J.W. (2022). Lithosepermic Acid Restored the Skin Barrier Functions in the Imiquimod-Induced Psoriasis-like Animal Model. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116172"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Guo, J.W., Cheng, Y.P., Liu, C.Y., Thong, H.Y., Huang, C.J., Lo, Y., Wu, C.Y., and Jee, S.H. (2020). Salvianolic Acid B in Microemulsion Formulation Provided Sufficient Hydration for Dry Skin and Ameliorated the Severity of Imiquimod-Induced Psoriasis-Like Dermatitis in Mice. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12050457"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"154","DOI":"10.22270\/jddt.v9i3.2630","article-title":"Development and Validation of RP-HPLC Method for Desoximetasone in Bulk and Cream Formulation","volume":"9","author":"Gorle","year":"2019","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_20","first-page":"337","article-title":"Topical Corticosteroids: Choice and Application","volume":"103","author":"Stacey","year":"2021","journal-title":"Am. Fam. Physician"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1166\/jbn.2021.3202","article-title":"A Nanocrystals-Based Topical Drug Delivery System with Improved Dermal Penetration and Enhanced Treatment of Skin Diseases","volume":"17","author":"Sun","year":"2021","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nastiti, C., Ponto, T., Abd, E., Grice, J.E., Benson, H.A.E., and Roberts, M.S. (2017). Topical Nano and Microemulsions for Skin Delivery. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9040037"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhang, L., Dong, Z., Liu, W., Wu, X., He, H., Lu, Y., Wu, W., and Qi, J. (2022). Novel Pharmaceutical Strategies for Enhancing Skin Penetration of Biomacromolecules. Pharmaceuticals, 15.","DOI":"10.3390\/ph15070877"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Alkilani, A.Z., Nasereddin, J., Hamed, R., Nimrawi, S., Hussein, G., Abo-Zour, H., and Donnelly, R.F. (2022). Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061152"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.jconrel.2022.09.025","article-title":"Overcoming skin barriers through advanced transdermal drug delivery approaches","volume":"351","author":"Phatale","year":"2022","journal-title":"J. Control Release"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.pharmthera.2012.12.007","article-title":"Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation","volume":"138","author":"Zanger","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/exd.13483","article-title":"Expression and enzyme activity of cytochrome P450 enzymes CYP3A4 and CYP3A5 in human skin and tissue-engineered skin equivalents","volume":"27","author":"Smith","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1001\/jama.2022.5270","article-title":"Psoriasis","volume":"327","author":"Walter","year":"2022","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1080\/14740338.2020.1749594","article-title":"Safety of calcipotriene and betamethasone dipropionate foam for the treatment of psoriasis","volume":"19","author":"Puig","year":"2020","journal-title":"Expert. Opin. Drug Saf."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/8\/2016\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:18:47Z","timestamp":1760127527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/8\/2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,25]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["pharmaceutics15082016"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15082016","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,25]]}}}