RESUMEN
The development of biocompatible polymeric nanoparticles has become an important strategy for optimizing the therapeutic efficacy of many classical drugs, as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. In this study, nanoparticles of Amphotericin B entrapped within poly (lactic-co-glycolic) acid and incorporated with dimercaptosuccinic acid (NANO-D-AMB) as a target molecule were evaluated for their physic-chemical characteristics, pharmacokinetics, biocompatibility and antifungal activity. We found high plasma concentrations of Amphotericin B upon treatment with NANO-D-AMB and a high uptake of nanoparticles in the lungs, liver and spleen. NANO-D-AMB exhibited antifungal efficacy against Paracoccidioides brasiliensis and induced much lower cytotoxicity levels compared to D-AMB formulation in vivo and in vitro. Together, these results confirm that NANO-D-AMB improves Amphotericin B delivery and suggest this delivery system as a potential alternative to the use of Amphotericin B sodium deoxycholate.
Asunto(s)
Anfotericina B/química , Anfotericina B/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Ácido Desoxicólico/química , Ácido Desoxicólico/farmacología , Portadores de Fármacos/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Anfotericina B/efectos adversos , Anfotericina B/uso terapéutico , Animales , Antifúngicos/efectos adversos , Antifúngicos/uso terapéutico , Ácido Desoxicólico/efectos adversos , Ácido Desoxicólico/uso terapéutico , Portadores de Fármacos/farmacocinética , Combinación de Medicamentos , Liberación de Fármacos , Ácido Láctico/farmacocinética , Ensayo de Materiales , Ratones , Paracoccidioides/efectos de los fármacos , Paracoccidioides/fisiología , Paracoccidioidomicosis/tratamiento farmacológico , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Seguridad , Succímero/química , Distribución TisularRESUMEN
AIMS: To evaluate the soybean polyphenol glucosides bioconversion to aglycone forms by different beta-glucosidases-producing filamentous fungi to enhance their antioxidant activity. METHODS AND RESULTS: Soybean defatted flour was submitted to solid-state fermentation with Aspergillus niger, Aspergillus niveus and Aspergillus awamori. The fungi studied produced approximately the same beta-glucosidase activity units amount when p-nitrophenyl-beta-d-glucopyranoside was used as substrate for the assay. However, electrophoretic analysis, using 4-methylumbellipheryl-beta-d-glucopyranoside as substrate, showed that beta-glucosidase produced by A. niveus was more active. Fermented methanolic extracts showed an increase in polyphenol and genistein contents and antioxidant activities. The highest genistein content was found in soybean fermented by A. niveus. Methanolic extracts of the soybean fermented by the different fungi showed a similar capacity of scavenging H(2)O(2) generated in vivo by the tumour promoter 12-O-tetradecanoyl phorbol-13-acetate. CONCLUSIONS: A. niveus synthesized a beta-glucosidase with higher specificity to hydrolyse genistin beta-glycosidic bond than those produced by A. awamori and A. niger. SIGNIFICANCE AND IMPACT OF THE STUDY: The utilization of these beta-glucosidases-producing fungi in soybean fermentation processes resulted in the obtaining of methanolic extracts with different antioxidant potentials that could be used either therapeutically or as an antioxidant in nonphysiological oxidative stress conditions, as the one induced in skin by UV radiation.