The role of topical nano-based drug delivery systems for acne treatment: A systematic review and translational insights

Abstract

Acne vulgaris predominantly affects sebaceous gland-rich areas, including the face, neck, upper chest, shoulders, and back. Its pathogenesis involves increased sebum production, abnormal follicular keratinization, Cutibacterium acnes-mediated inflammation, and immune responses. Topical therapy—such as benzoyl peroxide, retinoids, and antimicrobials—remains the first-line treatment for mild-to-moderate acne due to localized action and reduced systemic effects. However, antibiotic resistance, skin irritation, and poor adherence are limiting. This systematic review critically analyzes clinical evidence on topical nano-based drug delivery systems for acne, assessing clinical performance, safety, and their potential to address unmet therapeutic needs. Following PRISMA guidelines, searches of four databases retrieved 1,303 records, of which 23 met inclusion criteria (2012–2025; 1,341 participants). Primary outcomes included lesion count reduction (inflammatory, non-inflammatory, total), acne severity, sebum production, and safety/tolerability. Mechanistic pathways of nanomedicines in acne pathogenesis and translational barriers were also evaluated. Nanocarriers—as solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, nanocrystals, liposomes, and nanoemulsions—loaded with active pharmaceutical ingredients (APIs) or natural compounds demonstrated superior lesion reduction and faster onset of action compared to conventional formulations. Benefits were linked to enhanced follicular targeting, controlled release, and anti-inflammatory or sebostatic effects. Formulations containing synthetic APIs (e.g., tretinoin, adapalene, clindamycin) and natural actives (e.g., quercetin, mangostin, syringic acid, linoleic acid) showed comparable efficacy, with some natural compounds offering superior safety and patient acceptability. Topical nanomedicines present promising clinical advantages in acne management, potentially improving adherence and outcomes. Further large-scale, head-to-head trials are needed to confirm their role alongside standard therapies and support regulatory adoption.