Improved efficacy and safety of low doses of benznidazole-loaded multiparticulate delivery systems in experimental Chagas disease therapy.

Autor: García MC; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Ciencias Farmacéuticas, Ciudad Universitaria, X5000HUA, Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA)-CONICET-UNC, Córdoba, Argentina. Electronic address: mgarcia@unc.edu.ar., Eberhardt N; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Ciudad Universitaria, X5000HUA, Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-CONICET-UNC, Córdoba, Argentina. Electronic address: natalia.eberhardt@nyulangone.org., Sanmarco LM; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Ciudad Universitaria, X5000HUA, Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-CONICET-UNC, Córdoba, Argentina. Electronic address: lsanmarco@bwh.harvard.edu., Ponce NE; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Ciudad Universitaria, X5000HUA, Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-CONICET-UNC, Córdoba, Argentina. Electronic address: nponce@fcq.unc.edu.ar., Jimenez-Kairuz AF; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Ciencias Farmacéuticas, Ciudad Universitaria, X5000HUA, Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA)-CONICET-UNC, Córdoba, Argentina. Electronic address: ajimenez-kairuz@unc.edu.ar., Aoki MP; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Ciudad Universitaria, X5000HUA, Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-CONICET-UNC, Córdoba, Argentina. Electronic address: paoki@fcq.unc.edu.ar.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2021 Sep 01; Vol. 164, pp. 105912. Date of Electronic Publication: 2021 Jun 13.
DOI: 10.1016/j.ejps.2021.105912
Abstrakt: Benznidazole (BZ) is a first-line drug for the treatment of Chagas disease; however, it presents several disadvantages that could hamper its therapeutic success. Multiparticulate drug delivery systems (MDDS) are promising carriers to improve the performance of drugs. We developed BZ-loaded MDDS intended for improving Chagas disease therapy. To assess their efficacy and safety, Trypanosoma (T) cruzi infected BALB/c mice were orally treated with free BZ or BZ-MDDS at different regimens (doses of 50 and 100 mg/kg/day, administered daily or at 2- or 5-days intervals) and compared with infected non-treated (INT) mice. At 100 mg/kg/day, independent of the administration regimen, both treatments were able to override the parasitemia, and at 50 mg/kg/day significantly reduced it compared to INT mice. BZ-MDDS at a dose of 100 mg/kg/day administered every 5 days (BZ-MDDS 100-13d) induced the lowest cardiac parasite load, indicating an improved efficacy with lower total dose of BZ when loaded to the MDDS. Reactive oxygen species produced by leukocytes were higher in INT and mice treated with BZ at 50 mg/kg/day compared to 100 mg/kg/day, likely because of persistent infection. BZ-MDDS treatments markedly reduced heart and liver injury markers compared to INT mice and those receiving the standard treatment. Therefore, BZ-MDDS exhibited enhanced activity against T. cruzi infection even at lower doses and reduced administration frequency compared to free BZ while increasing the treatment safety. They likely avoid undesired side effects of BZ by keeping a sustained concentration, avoiding plasmatic drug peaks. BZ-MDDS evidenced significant improvements in experimental Chagas disease treatment and can be considered as a potential improved therapeutic alternative against this illness.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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