Desenvolvimento de nanoemulsões e nanocápsulas poliméricas contendo tioconazol e incorporação em hidrogéis

Abstract

This work aimed to develop nanoemulsions and polymeric nanocapsules containing tioconazole for the topical treatment of superficial mycoses. Initially, a method was validated by liquid chromatography with UV detection to quantify the tioconazole in the nanostructured formulations. The method proved to be specific, linear, precise, accurate and robust. The nanoemulsions and tioconazole-loaded PCL nanocapsules (1.0 mg/mL) were prepared by spontaneous emulsification and interfacial deposition of preformed polymer methods, respectively, and using as oily core medium chain triglycerides or green coffee oil. The physicochemical parameters evaluated were: particle size, polydispersity index, pH, zeta potential, drug content and encapsulation efficiency. Formulations presented nanometric mean size (150-200 nm), polydispersity index below 0.15, acid pH (5.5 to 6.3), negative zeta potential (-3.5 to -11.3 mV), drug content close to the theoretical and encapsulation efficiency close to 100%. With the exception of pH, all these parameters remained the same after 30 days of storage, proving the stability of systems. The study of photodegradation of tioconazole against UVC light has shown the importance of nanostructured photoprotection in the drug and the greater protection was observed for the nanocapsules containing green coffee oil. The antifungal activity of the nanostructures was evaluated by agar diffusion and the results showed that the formulations presented antifungal activity against the yeast C. albicans, C. glabrata and clinical isolate of C. albicans. The nanostructures were incorporated into Aristoflex® AVC hydrogels and those were characterized by size of particles when dispersed in water, polydispersity index, drug content, spreadability, rheological properties and stability. The hydrogels had nanometer size (196-203 nm), polydispersity index below 0.25, pH 6,3 to 6.5, tioconazole content close to theoretical (0.99 to 1.01 mg/g) plastic behavior (model Casson) and similar spreadability profiles. The formulations were stable for 30 days at room temperature, evidencing the importance of the polymeric wall in the nanocapsules to preserve the characteristics of the formulations. The study of the in vitro release of drug from the hydrogel was carried out using diffusion Franz cell. The results demonstrated the ability of nanostructures to control the release of tioconazole, with greater control observed for hydrogels containing polymeric nanocapsules.