Melasma is a hard-to-treat hyperpigmentation disorder. Combined incorporation of kojic dipalmitate (KDP), the esterified form of kojic acid, and rosehip oil, an oil with antioxidant and skin-regenerating properties, into nanocarrier systems appears to be a suitable strategy to develop high-performance formulations. A high-energy method (Ultra-Turrax^®) was used to develop nanoemulsions containing up to 2 mg/mL KDP, 5% rosehip oil, and 7.5% surfactant. Formulations were characterized regarding droplet size, size distribution, pH, density, morphology, KDP content, incorporation efficiency, and stability under different temperature conditions. A scale-up study was conducted. Skin permeation, antioxidant potential, and tyrosinase inhibitory activity were assessed in vitro. Cell viability studies were also performed. Results showed that nanoemulsions containing 1 and 2 mg/mL KDP had incorporation efficiencies greater than 95%, droplet size smaller than 130 nm, suitable size distribution, zeta potential of approximately −10 mV, and good stability over 30 days of refrigerated storage. The nanoemulsion containing 1 mg/mL KDP was chosen for further evaluation because it had lower nanocrystal formation, greater scale-up feasibility and allowed KDP permeation up to the epidermis similarly than observed for 2 mg/mL KDP. This formulation (1 mg/mL KDP) showed antioxidant and depigmenting efficacy, close to that of 1 mM ascorbic acid. No cytotoxicity was observed in formulations concentrations ranging from 0.06% to 1%.

Ozone is a strong oxidizing agent, capable of promoting therapeutic effects such as antimicrobial, anti inflammatory, antioxidant and healing activities, with low probability of toxicity when used in a specific dosage range. The aim of this study was to conduct a literature review to assess clinical trials available over the past 10 years regarding the effectiveness and safety of ozone therapy to treat dermatological disorders. The search for bibliographic material was carried out through PubMed, Cochrane Library and Google Scholar electronic databases. The inclusion criteria covered only controlled clinical trials published from 2011 to 2021 and written in English. The 18 selected clinical trials included 1279 patients (ranging from 12 to 400 patients per study), of which 1185 patients were adults and 94 were children. Ozone therapy was evaluated regarding the treatment of diabetic foot ulcers, digital ulcers, chronic venous leg ulcers, atopic dermatitis, skin burns, onychomycosis, tinea pedis, cutaneous leishmaniasis, balanitis xerotica obliterans and multiple common warts. Only three studies, addressing the treatment of cutaneous leishmaniasis, skin ulcers and skin burns, evidenced lack of effectiveness of ozone treatment. Mild adverse effects occurred in three clinical trials, whereas severe side effects occurred in only one clinical trial, regarding skin ulcers. Therefore, ozone therapy may be suggested as an alternative or complementary treatment in some types of dermatological conditions specially affecting refractory patients. Though, a greater number of high-quality clinical trials is needed to clearly establish the safety of ozone therapy in dermatological disorders.