CLOBETASOL PROPIONATE NANOCRYSTALS: IMPROVING DRUG SAFETY FOR TOPICAL APPLICATION

Resumo

INTRODUCTION: Inflammatory skin diseases can cause symptoms such as pain, redness, itching, and scaling, resulting from the interaction of genetic, environmental, and immunological factors. Clobetasol propionate (CP) is used as a topical treatment, but prolonged use may cause side effects. Nanotechnology is a promising alternative to improve efficacy and reduce toxicity. MATERIALS AND METHODS: CP nanocrystals (NC-CP) were developed by precipitation–ultrasonication using acetone as a solvent and HPMC as stabilizer. The samples were characterized in triplicate of batches regarding average particle size and size distribution, pH, zeta potential, drug content, nanocrystallization rate, and stability. In vitro release assays (dialysis bag) and skin permeation (Strat-M® membrane) were also performed, comparing NC-CP with CP classical solutions used to formulate clobetasol topical products: ethanol and propylene glycol. The cytotoxicity was evaluated (MTT and neutral red [NR] assays on 3T3 cells) comparing NC-CP with the drug solution in DMSO. RESULTS AND DISCUSSION: The nanocrystals presented average size of 648 ± 67.77 nm and a PDI of 0.317 ± 0.05, drug content of 90.29%, nanocrystallization rate of 99.36%, and pH of 7.53, maintaining stability for 180 days under refrigeration. Microscopy images confirmed the efficacy of the nanocrystallization process. NC-CP showed controlled CP release over 48 h, with significantly lower CP released values than drug solution (p < 0.05). Regarding permeation to the receptor fluid, NC-CP presented significantly lower values of permeated CP than the drug solutions (24 h and 48 h; p < 0.05). These data suggest CP retention in viable layers, with reduced chance of systemic effects. NC-CP cytotoxicity assays showed viability above 80%, except at the highest nanocrystal concentration (0.5 mg/mL) in the MTT test. The drug solution, on the other side, showed cellular viability values of less than 40% (MTT) and less than 60% (NRU) for all concentrations tested. CONCLUSION: NC-CP was considered promising for topical application, offering controlled release, reduced skin permeation and citocompatibility, supporting its improvement of drug safety in the topical treatment of inflammatory skin diseases.