Metal oxide nanoparticles for acne vulgaris: mechanisms, synthesis, formulation, and translational prospects

Acne vulgaris is a chronic inflammatory condition of the pilosebaceous unit resulting from follicular hyperkeratinization, increased sebum production, overgrowth of Cutibacterium acnes, and immune activation, with subsequent activation of Toll-like receptor signalling and increased expression of IL-1β, IL-8, and matrix metalloproteinases, leading to scarring and hyperpigmentation. Conventional treatments such as topical retinoids, benzoyl peroxide, antibiotics, oral isotretinoin, and hormonal therapies are often associated with limited efficacy, slow response, irritation, photosensitivity, and poor tolerability, prompting the search for non-antibiotic strategies that preserve the microbiome. This review evaluates metal oxide nanoparticles as multifunctional agents with acne-targeted, anti-inflammatory, antioxidant, and photocatalytic activities suitable for the follicular microenvironment. The emphasis is placed on zinc oxide, titanium dioxide, copper oxide, iron oxide, magnesium oxide, cerium oxide, aluminium oxide and manganese oxide nanoparticles. The review further examines synthesis methods (physical, wet-chemical, and green plant/microbial synthesis), formulation platforms (hydrogels/nanogels, electrospun fibers, lipid carriers, microneedles, and near-infrared (NIR)-responsive nanomotors), as well as safety and regulatory aspects. Available evidence suggests that primary particle size (typically 20-70 nm), hydrodynamic aggregation (200-700 nm for follicular depots), zeta potential (-10 to -30 mV), and surface coatings (e.g., hyaluronic acid, polysaccharides, and polyethylene glycol (PEG)) significantly influence dermal fate. Metal oxide nanoparticles represent promising adjuvants and potential alternatives for the treatment of mild-to-moderate acne vulgaris and maintenance therapy, provided they are synthesized using standardized protocols, formulated through microbiome-friendly approaches, toxicologically evaluated using harmonized assessment frameworks, and validated through rigorous, adequately powered clinical trials.