RESUMEN
Amphotericin B (AmB) is one of the most used drugs for the treatment of systemic fungal infections; however, the treatment causes several toxic manifestations, including nephrotoxicity and hemolytic anemia. Chitosan-coated poly(lactide-co-glycolide) (PLGA) nanoparticles containing AmB were developed with the aim to decrease AmB toxicity and propose the oral route for AmB delivery. In this work, the antifungal efficacy of chitosan-coated PLGA nanoparticles containing AmB was evaluated in 20 strains of fungus isolates from patients with vulvovaginal candidiasis (01 Candida glabrata and 03 Candida albicans), bloodstream infections (04 C. albicans and 01 C. tropicalis) and patients with urinary tract infection (04 Candida albicans, 02 Trichosporon asahii, 01 C. guilhermondii, 03 C. glabrata) and 01 Candida albicans ATCC 90028. Moreover, the cytotoxicity over erythrocytes was evaluated. The single-emulsion solvent evaporation method was suitable for obtaining chitosan-coated PGLA nanoparticles containing AmB. Nanoparticles were spherical in shape, presented mean particle size about 460 nm, positive zeta potential and encapsulation efficiency of 42%. Moreover, nanoparticles prolonged the AmB release. All the strains were susceptible to plain AmB and nanostructured AmB, according to EUCAST breakpoint version 8.1 (resistant > 1 µg/mL), using broth microdilution method. In C. albicans (urine, blood, and vulvovaginal secretion isolates, and 1 ATCC), the MIC value of AmB-loaded nanoparticles varied from 0.25 to 0.5 µg/mL and EUCAST varied from 0.03 to 0.5 µg/mL. In urine and vulvovaginal secretion isolates of C. glabrata, the MIC value of AmB-loaded nanoparticles varied from 0.25 to 0.5 µg/mL and EUCAST varied from 0.03 to 0.015 µg/mL. In urine isolates of C. guilhermondii, the MIC value of AmB-loaded nanoparticles was 0.12 µg/mL and EUCAST was 0.06 µg/mL. In blood isolates of C. tropicalis, the MIC value of AmB-loaded nanoparticles was 0.5 µg/mL and EUCAST was 0.25 µg/mL. Finally, in urine isolates of T asahii, the MIC value of AmB-loaded nanoparticles was 1 µg/mL and EUCAST varied from 0.5 to 1 µg/mL. In the cytotoxicity assay, plain AmB was highly hemolytic (100% in 24 h) while AmB-loaded chitosan/PLGA nanoparticles presented negligible hemolysis.
Asunto(s)
Anfotericina B/farmacología , Antifúngicos/farmacología , Candida/efectos de los fármacos , Quitosano/metabolismo , Portadores de Fármacos/metabolismo , Ácido Láctico/metabolismo , Ácido Poliglicólico/metabolismo , Trichosporon/efectos de los fármacos , Animales , Candida/aislamiento & purificación , Candidemia/microbiología , Candidiasis Vulvovaginal/microbiología , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Nanopartículas/metabolismo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Trichosporon/aislamiento & purificación , Infecciones Urinarias/microbiologíaRESUMEN
Neglected diseases are prevalent in less developed countries and are associated with high levels of mortality and/or morbidity. The drugs used in clinical practice are toxic, reducing patient compliance, and generally do not result in a cure, and there has also been a surge in drug resistance. Additionally, a major challenge in drug treatment lies in reaching the intracellular sites infected by parasites. The development of nanotechnology-based drug delivery systems for drugs intended to treat neglected diseases is a promising avenue because the use of nanocarriers presents the ability to target drugs to the infected cells, and the prolonged drug release profile possible with these systems permits longer contact between the drug and the parasite. This review describes the roles of colloidal drug carriers, such as liposomes, polymeric nanoparticles and solid lipid nanoparticles, in research on optimizing the delivery of antileishmanial, antitrypanosomal, antichagasic and antimalarial agents.