Azelaic acid-loaded nanoemulsion with hyaluronic acid - a new strategy to treat hyperpigmentary skin disorders.

OBJECTIVE: To develop an azelaic acid (AzA)-loaded nanoemulsion with hyaluronic acid (HA) as a double targeting strategy to increase drug retention and tyrosinase inhibition activity. SIGNIFICANCE: Dermic melasma is a recalcitrant disease. Therefore, the development of new technologies that allow a deeper penetration in the skin while enhancing the efficacy of a safe and well-known dermatological active, like AzA, is a very promising alternative to improve the treatment of this disease. METHODS: An oil-in-water nanoemulsion was developed and characterized according to its droplet size distribution, zeta potential, pH value, drug content, encapsulation efficiency, spectroscopic characteristics, morphology, and stability. In vitro mushroom tyrosinase inhibition assay, cytotoxicity, and permeation studies were performed. A descriptive sensory evaluation was also carried out. RESULTS: Drug content was 10 mg/ml, particle size 419 ± 23 nm with monomodal distribution, encapsulation efficiency was 84.65%, zeta potential -10.9 ± 0.44 mV and pH 5.01 ± 0.01. The nanoemulsion was stable for 30 days (30 °C/65% RH). The nanoemulsion decreased tyrosinase activity and permeated through the skin, reaching viable epidermis and dermis and did not show signs of cytotoxicity. Sensory evaluation profile showed a higher spreadability with lesser whitening residue. CONCLUSION: The nanoemulsion presented characteristics within the nanoscale and reached the deeper layers of the skin while improving in vitro tyrosinase inhibition; hence, it could be a promising treatment to dermic melasma.

Development of a Clioquinol Nanocarrier as a New, Promising Option for the Treatment of Dermatomycosis.

Dermatomycosis is a common fungal infection, and its treatment is limited by few antifungal agents. Clioquinol (CQ) is an antiparasitic agent that has been studied for new uses, such as antifungal and antiviral applications. CQ was incorporated into a lipid-based nanocarrier as a new, promising option for dermatomycosis. This study aimed to develop a CQ-loaded lipid-based nanocarrier for cutaneous application and to evaluate its antifungal activity. CQ-loaded nanoformulation (LBN-CQ) was developed using the ultrasonication method, and the particle size, polydispersity index (PDI), pH, zeta potential, and drug content were monitored for 45 days. To evaluate antifungal activity, broth microdilution and a time-kill assay were performed. LBN-CQ presented a particle size of 91 ± 3 nm and PDI of 0.102 ± 0.009. The zeta potential and pH values were -9.7 ± 2.0 mV and 6.0 ± 0.1, respectively. The drug content was 96.4 ± 2.3%, and the encapsulation efficiency was 98.4%. LBN-CQ was able to reduce the minimum inhibitory concentration (MIC) in a 2-fold or 4-fold manner in most of the tested strains. Additionally, LBN-CQ presented stable fungistatic action that was not concentration- or time-dependent. In conclusion, the developed CQ-loaded nanocarrier is a promising treatment for skin fungal infections and a promising candidate for future randomized clinical trials.

Chloroacetamide derivatives as a promising topical treatment for fungal skin infections.

The aim of this study was to evaluate the antifungal potential of 11 chloroacetamide derivatives and derivative incorporated into a film-forming system (FFS) as a potential alternative for the topical treatment of superficial and skin mycoses. The minimum inhibitory concentration (MIC) evaluation followed Clinical and Laboratory Standards Institute protocols M27-A3 (Candida) and M28-A2 (dermatophytes). Compounds 2, 3, and 4 were the most effective against Candida species (MIC range: 25-50 µg/mL) and dermatophytes (MIC range: 3.12-50 µg/mL). Compound 2 maintained its antifungal activity when incorporated in a FFS, with MIC values equivalent to the free compound. In addition, the compound does not act through complexation with ergosterol, suggesting that it may act on other targets of the fungal cell membrane. Chloroacetamide derivatives presented anti-Candida and anti-dermatophytic effectiveness. The FFS containing compound 2 has shown to be superior to traditional topical treatment of superficial and cutaneous fungal infections. It was found that these new chemical entities, with their applicability, are an excellent alternative to the topical treatment of fungal skin infections.