Add time:07/26/2019         Source:sciencedirect.com

Leucinostatin A (Leu-A) is a nonapeptide exerting a remarkable activity especially against Candida albicans and Cryptococcus neoformans; nevertheless, its employment is limited due its toxicity. Therefore, we recently developed liposomal formulations, as suitable delivery systems, in order to increase its therapeutic index. However, liposomes present disadvantages related to their long-term instability. For this reason poly(lactic-co-glycolic) nanospheres (NS) were chosen as alternative colloidal carriers for Leu-A delivery. NS were formulated by spontaneous emulsification solvent diffusion method. This study investigates the effects of different parameters on drug encapsulation efficiency and particle size as well. The best preparation obtained was also characterized for its in vitro release, in vivo acute toxicity (LD50), and effectiveness against C. albicans in mice. In vitro release was performed over 100 h and resulted sufficiently sustained with more than 93% of the peptide released. Acute toxicity showed that the LD50 was increased more than 18-fold and the study on systemic candidiasis models revealed high effectiveness of the NS in reducing either the growth of fungal colonies in infected mice liver or in the mortality index. In conclusion, we can propose that Leu-A loaded NS could represent a new promising therapeutic system against Candida infection.

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