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

Polymers

卷:14

Rodica Tatia¹  Carmen Lacramioara Zamfir²  Alexandra-Simona Zamfir³  Luminita Confederat⁴  Catalina Daniela Stan⁵  Andreea Teodora Iacob⁵  Maria Dragan⁵  Oana-Maria Dragostin⁶  Ionut Dragostin⁶  Carmen Lidia Chitescu⁶ 

[1] Department of Cellular and Molecular Biology, National Institute of Research and Development for Biological Sciences, 296 Splaiul Independentei, 060031 Bucharest, Romania;

[2] Department of Histology, Faculty of Medicine, University of Medicine and Pharmacy Grigore T. Popa, 16 Universitatii Str., 700115 Iasi, Romania;

[3] Department of Pneumology, Faculty of Medicine, University of Medicine and Pharmacy Grigore T. Popa, 16 Universitatii Str., 700115 Iasi, Romania;

[4] Faculty of Medicine, University of Medicine and Pharmacy Grigore T. Popa, 16 Universitatii Str., 700115 Iasi, Romania;

[5] Faculty of Pharmacy, University of Medicine and Pharmacy Grigore T. Popa, 16 Universitatii Str., 700115 Iasi, Romania;

[6] Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, Dunarea de Jos University, 35 Al. I. Cuza Str., 800017 Galati, Romania;

关键词: encapsulation;    microparticles;    isoniazid derivatives;    chitosan;    drug toxicity;    biocompatibility;   

DOI  :  10.3390/polym14122310

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown