Iontophoresis-Based Topical Drug Delivery for Dermatologic Conditions: A Systematic Review

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.