Azole and 5-nitroimidazole based nanoformulations are potential antiamoebic drug candidates against brain eating amoebae.

Abstract

Herein, the anti-parasitic activity of azoles (fluconazole and itraconazole) and 5-nitroimdazole (metronidazole) against brain eating amoebae: Naegleria fowleri and Balamuthia mandrillaris was elucidated. Azoles and 5-nitroimdazole based nanoformulations were synthesized and characterized using UV-visible spectrophotometer, atomic force microscopy and fourier transform infrared spectroscopy. H1-NMR, EI-MS and ESI-MS were performed to determine their molecular mass and elucidate their structures. Their size, zeta potential, size distribution and polydispersity index were assessed. Amoebicidal assays revealed that all the drugs and their nanoformulations, (except itraconazole) presented significant anti-amoebic effects against B. mandrillaris, while all the treatments indicated notable amoebicidal properties against N. fowleri. Amoebicidal effects were radically enhanced upon conjugating the drugs with nanoparticles. The IC50 values for KM-38-AgNPs-F, KM-20-AgNPs-M and KM-IF were 65.09µg.mL-1, 91.27µg.mL-1 and 72.19µg.mL-1 respectively against B. mandrillaris. Whereas against N. fowleri, IC50 values were: 71.85µg.mL-1, 73.95µg.mL-1, and 63.01µg.mL-1 respectively. Additionally, nanoformulations significantly reduced N. fowleri mediated host cell death, while nanoformulations along with fluconazole and metronidazole considerably reduced Balamuthia mediated human cell damage. Finally, all the tested drugs and their nanoformulations revealed limited cytotoxic activity against human cerebral microvascular endothelial cell (HBEC-5i) cells. These compounds should be developed into novel chemotherapeutic options for use against these distressing infections due to free-living amoebae, as currently there are no effective treatments.