Hydrolyzed Galactomannan-Modified Nanoparticles and Flower-Like Polymeric Micelles for the Active Targeting of Rifampicin to Macrophages

• Autores: Moretton, Marcela Analía; Chiappetta, Diego Andrés; Andrade, Fernanda; Das Neves, José; Ferreira, Domingos; Sarmento, Bruno; Sosnik, Alejandro Dario
• Año de publicación: 2013
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: TUBERCULOSIS; CHITOSAN NANOPARTICLES; FLOWER-LIKE POLYMERIC MICELLES; HYDROLYZED GALACTOMANNAN; RIFAMPICIN; ACTIVE DRUG TARGETING TO MACROPHAGES
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Inhalable nanocarriers that are uptaken by macrophages represent an appealing approach for the targeting of antibiotics to the tuberculosis reservoir. In the present work, we report on the development of rifampicin (RIF)-loaded nanoparticles and flower-like polymeric micelles surface-modified with hydrolyzed galatomannan (GalM-h), a polysaccharide of mannose and galactose, two sugars that are recognized by lectin-like receptors. Initially, pure or GalM-h-associated chitosan nanoparticles (NPs) were produced by ionotropic gelation. Despite the composition, NPs displayed positive zeta potential values between +18.0 and +24.5 mV and a size ranging between 263 and 340 nm. In addition, RIF payloads were approximately 1.0% w/w. To increase the encapsulation efficiency, a more complex nanocarrier based on poly(epsilon-caprolactone)-b-poly(ethylene-glycol)-b-poly(epsilon-caprolactone) flower-like polymeric micelles (PMs) coated with chitosan or GalM-h/chitosan were engineered. These polymeric micelles displayed a bimodal size distribution with a positive zeta potential between +6.7 and +8.1 mV. More importantly, the drug encapsulation capacity was increased 12.9-fold with respect to the NPs. An agglutination assay with concanavalin A confirmed the presence of GalM-h on the surface. Qualitative uptake studies by fluorescence microscopy revealed that GalM-h-modified systems were taken-up by RAW 264.7 murine macrophages. Finally, the intracellular/cell associated levels of RIF following the incubation of cells with free or encapsulated drug indicated that while chitosan hinders the uptake, GalM-h leads to a significant increase of the intracellular concentration.
Fil: Moretton, Marcela Analía. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;
Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;
Fil: Andrade, Fernanda. Universidad de Porto; Portugal;
Fil: Das Neves, José. Universidad de Porto; Portugal; Instituto Superior de Ciências da Saúde-Norte. Department of Pharmaceutical Sciences. Health Sciences Research Center; Portugal;
Fil: Ferreira, Domingos. Universidad de Porto; Portugal;
Fil: Sarmento, Bruno. Universidad de Porto; Portugal; Instituto Superior de Ciências da Saúde-Norte. Department of Pharmaceutical Sciences. Health Sciences Research Center; Portugal;
Fil: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;