Desenvolvimento de formulação farmacêutica nanoestruturada contendo metronidazol para o tratamento tópico de tricomonose bovina

Abstract

Bovine trichomoniasis is a disease with significant reproductive impact, whose treatment presents limitations related to drug bioavailability and residence time at the site of action. In this context, chitosan-based nanoparticulate systems represent a promising strategy to optimize drug release and local retention. The present study aimed to develop and optimize chitosan nanoparticles containing metronidazole (MTZ), obtained by ionic gelation with sodium tripolyphosphate (TPP), evaluating the influence of synthesis conditions on encapsulation efficiency, loading capacity, and physicochemical properties of the system. Different MTZ incorporation strategies were compared, and the best performance was observed when the drug was previously added to the chitosan solution ([Q+MTZ]+TPP), reaching an encapsulation efficiency of 45% ± 0.28. Physicochemical characterization demonstrated the formation of nanoparticles with mean hydrodynamic diameters ranging from 148 to 174 nm, polydispersity index values below 0.3 for most formulations, and positive zeta potential, consistent with the protonation of chitosan amino groups in acidic medium. Increasing the initial MTZ concentration promoted a significant increase in hydrodynamic diameter and a progressive reduction in encapsulation efficiency, suggesting an intrinsic limitation of the encapsulation process, possibly associated with saturation of electrostatic interaction sites among the drug, chitosan, and TPP. Although statistically significant differences were observed among formulations regarding loading capacity, the obtained values were considered low, indicating limitations for future in vivo applications. The results demonstrate that drug incorporation conditions and initial concentration exert a determining influence on the structural properties and encapsulation performance of chitosan nanoparticles, providing support for the rational development of nanostructured systems intended for the controlled release of metronidazole.