Chitosan Microparticles Loaded with New Non-Cytotoxic Isoniazid Derivatives for the Treatment of Tuberculosis: In Vitro and In Vivo Studies

Abstract

Lately, in the world of medicine, the use of polymers for the development of innovative therapies seems to be a major concern among researchers. In our case, as a continuation of the research that has been developed so far regarding obtaining new isoniazid (INH) derivatives for tuberculosis treatment, this work aimed to test the ability of the encapsulation method to reduce the toxicity of the drug, isoniazid and its new derivatives. To achieve this goal, the following methods were applied: a structural confirmation of isoniazid derivatives using LC-HRMS/MS; the obtaining of microparticles based on polymeric support; the determination of their loading and biodegradation capacities; in vitro biocompatibility using MTT cell viability assays; and, last but not least, in vivo toxicological screening for the determination of chronic toxicity in laboratory mice, including the performance of a histopathological study and testing for liver enzymes. The results showed a significant reduction in tissue alterations, the disappearance of cell necrosis and microvesicular steatosis areas and lower values of the liver enzymes TGO, TGP and alkaline phosphatase when using encapsulated forms of drugs. In conclusion, the encapsulation of INH and INH derivatives with chitosan had beneficial effects, suggesting a reduction in hepatotoxicity and, therefore, the achievement of the aim of this paper.