Aim: Octyl gallate (OG) loaded into a nanostructured lipid system (NLS) was tested for antifungal activity and in vitro and in vivo toxicity. Methods & Results: The features of NLS-OG were analyzed by dynamic light scattering and showed adequate size (132.1 nm) and homogeneity (polydispersity index = 0.200). OG was active against Paraccoccidioides spp., and NLS-OG did not affect antifungal activity. NLS-OG demonstrated reduced toxicity to lung cells and zebrafish embryos compared with OG, whereas NLS was toxic to hepatic cells. OG and NLS-OG did not show toxicity in a Galleria mellonella model at 20 mg/kg. All toxic concentrations were superior to MIC (antifungal activity). Conclusion: These results indicate good anti-Paracoccidioides activity and low toxicity of NLS-OG.
Keywords: antifungal activity; nanoparticles; nonconventional animal models; systemic mycosis; toxicity.
Plain language summary Drugs for the treatment of fungal diseases are limited in number and present side effects, drug interactions, risks for pregnant women and fungal resistance. The authors produced a derivative compound from plants called octyl gallate (OG) and then incorporated it into a nanoparticle lipid system (NLS) for better distribution in biological fluids. NLS-OG was tested against a fungus called Paracoccidioides, which causes lung infections. The toxicity profile of NLS-OG was also evaluated in lung and hepatic cells as well as novel animal models. NLS-OG presented good antifungal activity and low toxicity in lung cells and embryos.