PURPOSE: To achieve prolonged drug release for the treatment of multidrug resistant tuberculosis and to improve the patient compliance, ethionamide loaded PLGA nanoparticles were developed. MATERIAL AND METHODS: They were developed by solvent evaporation method and optimized. The optimized formulation was subjected to various physico-chemical characterization, in vitro release studies and in vivo tolerability study. RESULTS AND DISCUSSION: There was no significant drug-polymer interaction and drug was encapsulated as crystalline form in nanoparticles. In vitro release was sustained up to 15 days in various media. Ethionamide loaded nanoparticles in mice did not reveal any statistically significant treatment related effects on body weight gain and clinical signs. Likewise, no treatment-related toxic effect was found in hematology, clinical chemistry and histopathology. Our results indicate the development of an orally effective safe formulation of ethionamide with sustained release property. CONCLUSION: Hence, ethionamide loaded nanoparticles offer excellent potential for further preclinical and clinical studies.
PURPOSE: To achieve prolonged drug release for the treatment of multidrug resistant tuberculosis and to improve the patient compliance, ethionamide loaded PLGA nanoparticles were developed. MATERIAL AND METHODS: They were developed by solvent evaporation method and optimized. The optimized formulation was subjected to various physico-chemical characterization, in vitro release studies and in vivo tolerability study. RESULTS AND DISCUSSION: There was no significant drug-polymer interaction and drug was encapsulated as crystalline form in nanoparticles. In vitro release was sustained up to 15 days in various media. Ethionamide loaded nanoparticles in mice did not reveal any statistically significant treatment related effects on body weight gain and clinical signs. Likewise, no treatment-related toxic effect was found in hematology, clinical chemistry and histopathology. Our results indicate the development of an orally effective safe formulation of ethionamide with sustained release property. CONCLUSION: Hence, ethionamide loaded nanoparticles offer excellent potential for further preclinical and clinical studies.
Authors: Elisabetta Pancani; Mario Menendez-Miranda; Alexandra Pastor; François Brisset; Marie-Françoise Bernet-Camard; Didier Desmaële; Ruxandra Gref Journal: Acta Pharm Sin B Date: 2018-03-27 Impact factor: 11.413