DSETHVASAN: A NOVEL NANODRUG AGAINST SLEEPING SICKNESS

Abstract

Sleeping sickness (causal agent, Trypanosoma sp. parasite) causes huge morbidity and mortality in Africa (both human and livestock) in particular and zoo animals worldwide. Three of the four currently approved drugs (Pentamidine, Melarsoprol, Eflornithine, and Nifurtimox) were developed over 50 years ago. Current therapies are unsatisfactory due to unacceptable level of side effects. Pentamidine, an aromatic diamidine, safest so far, inhibits mitochondrial enzymes. Furthermore, it is effective only in early stages of infections and not on the later stage. Melarsoprol, practically insoluble in water, is very toxic and it is given intravenously (i.v.) for later stage infections only. Other drugs like eflornithine and nitfurtimox are also unsatisfactory for various reasons. Human serum derived high-density lipoprotein (HDL; not mouse or any other mammalian HDL) shows trypanolytic effect in vitro and in vivo on T. brucei. But the mechanism of action of human HDL is far from clear. In the absence of novel drug leads, nanodrugs might be valid options as nanoparticles show better accessibility to cells, supramolecular interactions due to enormous increase in surface area to volume ratio, altered partition coefficient, etc. Surface-modified hydrophobic microsilica (FS), mixture of micro- and nanosilica (Dsethvasan) and nanosilica (AL) were characterized by UV–Vis, DLS, SEM, EDAX, AFM, and XRD. Trypanosoma evansi collected from infected horses were injected in mice. Control infected mouse (n = 30) showed 100% mortality within 72±24 h of injection. Dsethvasan-treated mice (n = 30) survived for 192±24 h. FS-treated mice (n = 30) survived for 120±24 h but the AL-treated mice (n = 30) died within 72±24 h of inoculation like infected control. Hydrophobic Dsethvasan which consists of pure amorphous forms of micro- and nanosilica works better than FS (AL is not at all effective). Therefore, micro- and nanomixture of amorphous silica is best suited for treating Trypanosoma infection in mice. The possible role of ratio of higher to lower size class has been discussed.