{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:06:25Z","timestamp":1790730385999,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1405215"],"award-info":[{"award-number":["U1405215"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriasis is an immune disease caused by rapid and incomplete differentiation of skin basal cells. Natural products such as indirubin have historically served as excellent sources for the treatments of psoriasis. However, the poor solubility and bioavailability due to its plane and rigid crystal structure, which limits its efficacy. Herein, to improve the efficacy of indirubin, a hydrogel-based microemulsion drug delivery system was developed for transdermal delivery. The mean droplet size of the optimized microemulsion was 84.37 nm, with a polydispersity index (PDI) less than 0.2 and zeta potential value of 0~\u221220 mV. The transdermal flux and skin retention of indirubin at 24 h were 47.34 \u00b1 3.59 \u03bcg\/cm2 and 8.77 \u00b1 1.26 \u03bcg\/cm2, respectively. The optimized microemulsion was dispersed in carbomer 934 hydrogel to increase the consistency. The indirubin-loaded microemulsion gel was tested on an imiquimod-induced psoriasis mouse model. Results showed that this preparation can improve psoriasis symptoms by down-regulating the expression of IL-17A, Ki67, and CD4+T. This experiment provides great scalability for researchers to treat psoriasis, avoid first-pass effects, and increase the concentration of targeted drugs.<\/jats:p>","DOI":"10.3390\/ijms23073798","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:22:14Z","timestamp":1648675334000},"page":"3798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Transdermal Delivery of Indirubin-Loaded Microemulsion Gel: Preparation, Characterization and Anti-Psoriatic Activity"],"prefix":"10.3390","volume":"23","author":[{"given":"Enxue","family":"He","sequence":"first","affiliation":[{"name":"School of Biomedical Science, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9188-7502","authenticated-orcid":false,"given":"Hailing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biomedical Science, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biomedical Science, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1536-634X","authenticated-orcid":false,"given":"Xunxun","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Biomedical Science, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Lei","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang 471023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-1906","authenticated-orcid":false,"given":"Yong","family":"Diao","sequence":"additional","affiliation":[{"name":"School of Biomedical Science, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMe2116301","article-title":"AhR Modulating Agent for the Topical Therapy of Plaque Psoriasis","volume":"385","author":"Bieber","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Georgescu, S.-R., Tampa, M., Caruntu, C., Sarbu, M.-I., Mitran, C.-I., Mitran, M.-I., Matei, C., Constantin, C., and Neagu, M. (2019). Advances in Understanding the Immunological Pathways in Psoriasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030739"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(20)32549-6","article-title":"Psoriasis","volume":"397","author":"Griffiths","year":"2021","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e20191397","DOI":"10.1084\/jem.20191397","article-title":"Interleukin-17 cytokines: Effectors and targets in psoriasis-A breakthrough in understanding and treatment","volume":"217","author":"Prinz","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00281-019-00766-z","article-title":"Resolution of plaque-type psoriasis: What is left behind (and reinitiates the disease)","volume":"41","author":"Benezeder","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Said, J., Elman, S., Perez-Chada, L., Mita, C., Merola, J., and LeBoeuf, N. (J. Am. Acad. Dermatol., 2022). Treatment of Immune Checkpoint Inhibitor-Mediated Psoriasis: A Systematic Review, J. Am. Acad. Dermatol., Online ahead of print.","DOI":"10.1016\/j.jaad.2022.02.030"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/j.drudis.2020.09.023","article-title":"Psoriasis: Pathological mechanisms, current pharmacological therapies, and emerging drug delivery systems","volume":"25","author":"Rapalli","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Huang, T., Lin, C., Alalaiwe, A., Yang, S., and Fang, J. (2019). Apoptotic or Antiproliferative Activity of Natural Products against Keratinocytes for the Treatment of Psoriasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102558"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.2174\/0929867323666160321121819","article-title":"Anti-Psoriasis Agents from Natural Plant Sources","volume":"23","author":"Bonesi","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1001\/jamadermatol.2018.2972","article-title":"Complementary and Alternative Medicine Therapies for Psoriasis: A Systematic Review","volume":"154","author":"Gamret","year":"2018","journal-title":"JAMA Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1111\/bjd.16807","article-title":"A traditional Chinese remedy points to a natural skin habitat: Indirubin (indigo naturalis) for psoriasis and the Malassezia metabolome","volume":"179","author":"Gaitanis","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.molimm.2018.07.011","article-title":"Indirubin ameliorates imiquimod-induced psoriasis-like skin lesions in mice by inhibiting inflammatory responses mediated by IL-17A-producing \u03b3\u03b4 T cells","volume":"101","author":"Xie","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/bjd.15894","article-title":"Comparison of indirubin concentrations in indigo naturalis ointment for psoriasis treatment: A randomized, double-blind, dosage-controlled trial","volume":"178","author":"Lin","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1517\/13543776.2015.1019865","article-title":"Indirubin derivatives: A patent review (2010\u2013present)","volume":"25","author":"Vougogiannopoulou","year":"2015","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104","DOI":"10.2174\/1574891X1302181106123659","article-title":"Nanomedicine Advances in Topical Infective and Non-Infective Skin Diseases Therapy","volume":"13","author":"Rahman","year":"2018","journal-title":"Recent Pat. Anti-Infect. Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1080\/17425247.2020.1758665","article-title":"Trends in nanotechnology-based delivery systems for dermal targeting of drugs: An enticing approach to offset psoriasis","volume":"17","author":"Saleem","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1080\/17425247.2016.1188801","article-title":"Current challenges and emerging drug delivery strategies for the treatment of psoriasis","volume":"13","author":"Hoffman","year":"2016","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"120829","DOI":"10.1016\/j.ijpharm.2021.120829","article-title":"Design, optimization and evaluation of a microemulsion-based hydrogel with high malleability for enhanced transdermal delivery of levamisole","volume":"605","author":"Hu","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4919","DOI":"10.2147\/IJN.S108765","article-title":"Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D-phospholipid complex","volume":"11","author":"Li","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e16125","DOI":"10.17795\/jjnpp-16125","article-title":"Design and Evaluation of Self-Emulsifying Drug Delivery System (SEDDS) Of Carvedilol to Improve the Oral Absorption","volume":"9","author":"Salimi","year":"2014","journal-title":"Jundishapur J. Nat. Pharm. Prod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.xphs.2016.10.001","article-title":"Recent Advances in Lipid-Based Vesicles and Particulate Carriers for Topical and Transdermal Application","volume":"106","author":"Jain","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/17425247.2020.1713087","article-title":"Permeation enhancers in transdermal drug delivery: Benefits and limitations","volume":"17","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"130","DOI":"10.2174\/1872211312666180227091059","article-title":"Development of Microemulsion Based Nabumetone Transdermal Delivery for Treatment of Arthritis","volume":"12","author":"Jagdale","year":"2018","journal-title":"Recent Pat. Drug Deliv. Formul."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.colsurfb.2015.03.062","article-title":"Nanoemulsions for dermal controlled release of oleanolic and ursolic acids: In vitro, ex vivo and in vivo characterization","volume":"130","author":"Alvarado","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1515\/acph-2017-0036","article-title":"Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: Physicochemical characterization and in vivo skin performance","volume":"67","author":"Vuleta","year":"2017","journal-title":"Acta Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"121488","DOI":"10.1016\/j.ijpharm.2022.121488","article-title":"Topical delivery of pharmaceutical and cosmetic macromolecules using microemulsion systems","volume":"615","author":"Macierzanka","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/j.xphs.2017.03.042","article-title":"Recent Update on Nanoemulgel as Topical Drug Delivery System","volume":"106","author":"Choudhury","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ju, Z., Sun, J., and Liu, Y. (2019). Molecular Structures and Spectral Properties of Natural Indigo and Indirubin: Experimental and DFT Studies. Molecules, 24.","DOI":"10.3390\/molecules24213831"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1080\/10717544.2017.1344333","article-title":"Fabrication, in-vitro characterization, and enhanced in-vivo evaluation of carbopol-based nanoemulsion gel of apigenin for UV-induced skin carcinoma","volume":"24","author":"Jangdey","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3109\/10717544.2013.866992","article-title":"Formulation of nanoemulsion: A comparison between phase inversion composition method and high-pressure homogenization method","volume":"22","author":"Kotta","year":"2015","journal-title":"Drug Deliv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.4049\/jimmunol.0802999","article-title":"Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23\/IL-17 axis","volume":"182","author":"Mourits","year":"2009","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.apsb.2017.02.002","article-title":"Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake","volume":"7","author":"Li","year":"2017","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1080\/10717544.2019.1689312","article-title":"Oral delivery of lycopene-loaded microemulsion for brain-targeting: Preparation, characterization, pharmacokinetic evaluation and tissue distribution","volume":"26","author":"Guo","year":"2019","journal-title":"Drug Deliv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.foodchem.2016.09.110","article-title":"Drug-in-cyclodextrin-in-liposomes as a carrier system for volatile essential oil components: Application to anethole","volume":"218","author":"Gharib","year":"2017","journal-title":"Food Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3798\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:46:32Z","timestamp":1760136392000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,30]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23073798"],"URL":"https:\/\/doi.org\/10.3390\/ijms23073798","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,30]]}}}