Inhalable Mannosylated Rifampicin-Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy.

Autor:	Galdopórpora JM; Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina., Martinena C; Facultad de Ciencias Exactas y Naturales, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires 1113, Argentina., Bernabeu E; Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina.; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1425, Argentina.; Instituto de Tecnología Farmacéutica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina., Riedel J; Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina.; Instituto de Tecnología Farmacéutica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina., Palmas L; Department of Scienze della Vita e dell'Ambiente, University of Cagliari, 09124 Cagliari, Italy., Castangia I; Department of Scienze della Vita e dell'Ambiente, University of Cagliari, 09124 Cagliari, Italy., Manca ML; Department of Scienze della Vita e dell'Ambiente, University of Cagliari, 09124 Cagliari, Italy., Garcés M; Departamento de Química Analítica y Fisicoquímica, Cátedra de Química General e Inorgánica, Facultad de Farmacia y Bioquímica, Instituto de Bioquímica y Medicina Molecular (IBIMOL), CONICET, Universidad de Buenos Aires, Buenos Aires 1113, Argentina., Lázaro-Martinez J; Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), CONICET, Universidad de Buenos Aires, Buenos Aires 1113, Argentina., Salgueiro MJ; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1425, Argentina., Evelson P; Departamento de Química Analítica y Fisicoquímica, Cátedra de Química General e Inorgánica, Facultad de Farmacia y Bioquímica, Instituto de Bioquímica y Medicina Molecular (IBIMOL), CONICET, Universidad de Buenos Aires, Buenos Aires 1113, Argentina., Tateosian NL; Facultad de Ciencias Exactas y Naturales, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires 1113, Argentina., Chiappetta DA; Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina.; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1425, Argentina.; Instituto de Tecnología Farmacéutica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina., Moretton MA; Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina.; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1425, Argentina.; Instituto de Tecnología Farmacéutica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina.
Jazyk:	angličtina
Zdroj:	Pharmaceutics [Pharmaceutics] 2022 Apr 28; Vol. 14 (5). Date of Electronic Publication: 2022 Apr 28.
DOI:	10.3390/pharmaceutics14050959
Abstrakt:	Among respiratory infections, tuberculosis was the second deadliest infectious disease in 2020 behind COVID-19. Inhalable nanocarriers offer the possibility of actively targeting anti-tuberculosis drugs to the lungs, especially to alveolar macrophages (cellular reservoirs of the Mycobacterium tuberculosis ). Our strategy was based on the development of a mannose-decorated micellar nanoformulation based in Soluplus ® to co-encapsulate rifampicin and curcumin. The former is one of the most effective anti-tuberculosis first-line drugs, while curcumin has demonstrated potential anti-mycobacterial properties. Mannose-coated rifampicin (10 mg/mL)-curcumin (5 mg/mL)-loaded polymeric micelles (10% w / v ) demonstrated excellent colloidal properties with micellar size ~108 ± 1 nm after freeze-drying, and they remain stable under dilution in simulated interstitial lung fluid. Drug-loaded polymeric micelles were suitable for drug delivery to the deep lung with lung accumulation, according to the in vitro nebulization studies and the in vivo biodistribution assays of radiolabeled (99mTc) polymeric micelles, respectively. Hence, the nanoformulation did not exhibit hemolytic potential. Interestingly, the addition of mannose significantly improved (5.2-fold) the microbicidal efficacy against Mycobacterium tuberculosis H37Rv of the drug-co-loaded systems in comparison with their counterpart mannose-free polymeric micelles. Thus, this novel inhaled nanoformulation has demonstrated its potential for active drug delivery in pulmonary tuberculosis therapy.
Databáze:	MEDLINE
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