Bridging the Gap Between Biological Potential and Clinical Efficacy of Topical Resveratrol: Advanced Delivery Systems and Nanotechnology-Based Approaches

Resveratrol (RSV) is a naturally occurring polyphenol with well-documented antioxidant, anti-inflammatory, antimicrobial, photoprotective, wound-healing, depigmenting, and anticancer properties, making it an attractive candidate for dermocosmetic and dermatological applications. However, its clinical translation into effective topical products remains limited by poor aqueous solubility, chemical instability, photoisomerization, rapid cutaneous metabolism, and restricted skin penetration, all of which compromise local bioavailability and therapeutic efficacy. This narrative review critically examines the molecular mechanisms underlying the cutaneous effects of RSV and discusses how its physicochemical and pharmacokinetic characteristics influence topical performance. Particular emphasis is placed on advanced delivery strategies developed to overcome these limitations, including lipid-based nanocarriers, polymeric nanoparticles (NPs), nanofibers, inorganic nanocarriers, microneedles, hydrogels, and other emerging delivery platforms. The mechanisms by which these systems improve RSV solubility, stability, controlled release, skin retention, and dermal penetration are critically evaluated together with their reported therapeutic outcomes. Although advanced delivery systems have consistently improved the topical performance of RSV in preclinical studies, clinical evidence remains limited. To date, only one published placebo-controlled clinical trial has specifically evaluated topical RSV as the active ingredient, and none of the advanced RSV-nanocarrier platforms discussed in this review has undergone clinical evaluation. Bridging this substantial translational gap will require not only further optimization of formulation design but also scalable manufacturing, rigorous clinical validation, and regulatory pathways capable of supporting the development of safe, effective and evidence-based next-generation dermocosmetic and dermatological products.