{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:18:17Z","timestamp":1792099097716,"version":"4.4.0"},"reference-count":28,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health\u2019s \u201cRicerca Corrente\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: The efficacy of topical therapies in dermatology is often limited by the barrier function of the stratum corneum, which restricts drug penetration. Iontophoresis is a non-invasive transdermal delivery technique that uses a low-intensity electrical current to enhance the transport of charged and polar molecules across the skin. It has emerged as a strategy to improve local drug bioavailability while minimizing systemic exposure. We systematically reviewed the clinical evidence on the efficacy, safety, and pharmacologic performance of iontophoresis-assisted topical drug delivery in dermatologic diseases. Methods: This systematic review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251234877). PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were searched through 19 November 2025 without language restrictions. Records were screened against predefined eligibility criteria, and data were extracted on study design, participants, dermatologic indications, intervention\/comparator, iontophoresis parameters, efficacy outcomes, and adverse events. The risk of bias was assessed using RoB 2 for randomized trials and the JBI checklist for non-randomized studies. Because of substantial clinical and methodological heterogeneity, the findings were synthesized narratively and no meta-analysis was performed. Results: Twenty-one studies published between 1990 and 2025 met the inclusion criteria, including 15 randomized and 6 non-randomized studies. Investigated conditions included psoriasis, eczema, melasma, post-inflammatory hyperpigmentation, herpes labialis, onychomycosis, chronic ulcers, systemic sclerosis-related digital ulcers, acne scarring, and actinic keratosis. Across studies, findings were mixed. The most consistent signals of benefit were observed in pigmentary disorders and infectious diseases, whereas results were more heterogeneous in inflammatory dermatoses and some studies did not show superiority over active comparators. Tolerability was generally favorable, with adverse events limited to mild, reversible local reactions such as erythema, tingling, burning, or transient irritation. No serious treatment-related adverse events were reported. Conclusions: Iontophoresis may represent a useful non-invasive delivery-enhancement strategy in selected dermatologic settings, particularly when topical efficacy is limited by anatomical or physicochemical barriers. However, heterogeneity in protocols, formulations, outcomes, and clinical indications limits direct comparison and does not support broad conclusions of efficacy across all dermatologic conditions. Larger, standardized trials are needed to clarify its therapeutic role, long-term efficacy, and indication-specific benefit.<\/jats:p>","DOI":"10.3390\/ph19050765","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"765","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Iontophoresis-Based Topical Drug Delivery for Dermatologic Conditions: A Systematic Review"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9495-6350","authenticated-orcid":false,"given":"Francesco","family":"Piscazzi","sequence":"first","affiliation":[{"name":"Dermatology Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3446-6648","authenticated-orcid":false,"given":"Francesco","family":"D\u2019Oria","sequence":"additional","affiliation":[{"name":"Dermatology Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alejandra","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Degree Course in Medicine and Surgery, Humanitas University, 20072 Pieve Emanuele, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Ardig\u00f2","sequence":"additional","affiliation":[{"name":"Dermatology Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4155\/tde.10.16","article-title":"Challenges and Opportunities in Dermal\/Transdermal Delivery","volume":"1","author":"Paudel","year":"2010","journal-title":"Ther. Deliv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.addr.2003.10.026","article-title":"Iontophoretic Drug Delivery","volume":"56","author":"Kalia","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2165\/00063030-200216050-00003","article-title":"Iontophoresis-Based Transdermal Delivery Systems","volume":"16","author":"Kanikkannan","year":"2002","journal-title":"BioDrugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3109\/1061186X.2015.1090442","article-title":"Transdermal Iontophoretic Drug Delivery: Advances and Challenges","volume":"24","author":"Ita","year":"2016","journal-title":"J. Drug Target."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/ics.12824","article-title":"Iontophoresis in Dermal Delivery: A Review of Applications in Dermato-cosmetic and Aesthetic Sciences","volume":"45","author":"Liatsopoulou","year":"2023","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"569","DOI":"10.4103\/ijdvl.IJDVL_185_16","article-title":"Methotrexate Iontophoresis versus Coal Tar Ointment in Palmoplantar Psoriasis: A Pilot Study","volume":"83","author":"Haseena","year":"2017","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e70054","DOI":"10.1111\/fcp.70054","article-title":"Treprostinil Iontophoresis in Diabetic Foot Ulcers: A Single Ascending Dose Safety Study","volume":"39","author":"Guigui","year":"2025","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_9","first-page":"45","article-title":"Successful Short-Term and Long-Term Treatment of Melasma and Postinflammatory Hyperpigmentation Using Vitamin C with a Full-Face Iontophoresis Mask and a Mandelic\/Malic Acid Skin Care Regimen","volume":"12","author":"Taylor","year":"2013","journal-title":"J. Drugs Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1365-4362.1995.tb04381.x","article-title":"New Treatment of Atrophic Acne Scars by Iontophoresis with Estriol and Tretinoin","volume":"34","author":"Schmidt","year":"1995","journal-title":"Int. J. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1046\/j.1365-4362.1999.00586.x","article-title":"Tretinoin-iontophoresis in Atrophic Acne Scars","volume":"38","author":"Schmidt","year":"1999","journal-title":"Int. J. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/1346-8138.13634","article-title":"Adjuvant Alternative Treatment with Chemical Peeling and Subsequent Iontophoresis for Postinflammatory Hyperpigmentation, Erosion with Inflamed Red Papules and Non-inflamed Atrophic Scars in Acne Vulgaris","volume":"44","author":"Kurokawa","year":"2017","journal-title":"J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2637691","DOI":"10.1155\/2018\/2637691","article-title":"Comparing the Efficacy of Triamcinolone Acetonide Iontophoresis versus Topical Calcipotriol\/Betamethasone Dipropionate in Treating Nail Psoriasis: A Bilateral Controlled Clinical Trial","volume":"2018","author":"Saki","year":"2018","journal-title":"Dermatol. Res. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/ajd.13228","article-title":"Iontophoretic Delivery of Methotrexate in the Treatment of Palmar Psoriasis: A Randomised Controlled Study","volume":"61","author":"Rangegowda","year":"2020","journal-title":"Australas. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1086\/505872","article-title":"Iontophoretic Acyclovir Cold Sore Study Group. Topical Iontophoretic Administration of Acyclovir for the Episodic Treatment of Herpes Labialis: A Randomized, Double-Blind, Placebo-Controlled, Clinic-Initiated Trial","volume":"43","author":"Morrel","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.pdpdt.2017.01.184","article-title":"Efficacy of Iontophoresis-Assisted Ablative Fractional Laser Photodynamic Therapy with Short Incubation Time for the Treatment of Actinic Keratosis: 12-Month Follow-up Results of a Prospective, Randomised, Comparative Trial","volume":"18","author":"Choi","year":"2017","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/00006534-199801000-00015","article-title":"Venous Ulcers: Improved Healing by Iontophoretic Administration of Calcitonin Gene-Related Peptide and Vasoactive Intestinal Polypeptide","volume":"101","author":"Gherardini","year":"1998","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1002\/jcph.1574","article-title":"Treprostinil Hydrogel Iontophoresis in Systemic Sclerosis-Related Digital Skin Ulcers: A Safety Study","volume":"60","author":"Guigui","year":"2020","journal-title":"J. Clin. Pharma"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/clpt.2013.255","article-title":"Cutaneous Iontophoresis of Treprostinil in Systemic Sclerosis: A Proof-of-Concept Study","volume":"95","author":"Roustit","year":"2014","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1159\/000069943","article-title":"A Randomized, Double-Blind, Placebo-Controlled Trial of Vitamin C Iontophoresis in Melasma","volume":"206","author":"Huh","year":"2003","journal-title":"Dermatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1473-2165.2011.00599.x","article-title":"A Single-blinded Comparative Study between the Use of Glycolic Acid 70% Peel and the Use of Topical Nanosome Vitamin C Iontophoresis in the Treatment of Melasma","volume":"11","author":"Sobhi","year":"2012","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.2147\/DDDT.S472922","article-title":"Treatment of Melasma with Tranexamic Acid Essence Combined with Iontophoresis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"18","author":"Guo","year":"2024","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"456","DOI":"10.2340\/00015555-1537","article-title":"Randomized Controlled Observer-Blinded Treatment of Chronic Foot Eczema with Iontophoresis and Bath-PUVA","volume":"93","author":"Tupker","year":"2013","journal-title":"Acta Derm. Venereol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1111\/1523-1747.ep12874474","article-title":"Properties of Transdermal Histamine Iontophoresis: Differential Effects of Season, Gender, and Body Region","volume":"94","author":"Magerl","year":"1990","journal-title":"J. Investig. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/j.1365-2133.2005.06741.x","article-title":"Cutaneous Side-Effects of Transdermal Iontophoresis with and without Surfactant Pretreatment: A Single-Blinded, Randomized Controlled Trial","volume":"153","author":"Li","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0278-6915(00)00058-2","article-title":"Effect of Saline Iontophoresis on Skin Barrier Function and Cutaneous Irritation in Four Ethnic Groups","volume":"38","author":"Singh","year":"2000","journal-title":"Food Chem. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/j.1365-2133.2009.09414.x","article-title":"Iontophoretic Delivery of Terbinafine in Onychomycosis: A Preliminary Study: Iontophoretic Delivery of Terbinafine in Onychomycosis","volume":"162","author":"Amichai","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/5\/765\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:17:30Z","timestamp":1779455850000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/5\/765"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":28,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ph19050765"],"URL":"https:\/\/doi.org\/10.3390\/ph19050765","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]}}}