Novel microfilaricidal activity of nanosilver

Abstract

Purpose:The currently available drug repertoire against lymphatic filariasis, a major health hazard in the developing world, is inadequate and is fraught with serious limitations. Thus, the development of an effective antifilarial strategy has become a global research thrust mandated by the World Health Organization. Nanoparticles of silver endowed with antibacterial potency are known to induce apoptosis in eukaryotic cells. The present study was designed to investigate the possible microfilaricidal efficacy of silver nanoparticles and to establish the validity of apoptotic rationale in antifilarial drug designing. Methods: This report analyzed the effect of nanoparticles of silver as well as gold (size range: 10-15 nm) on the microfilariae of Brugia malayi obtained from the lavage of peritoneal cavities of infected jirds (Meriones unguiculatus). The study included a microfilarial motility assay, a trypan blue exclusion test, a poly(adenosine diphosphate-ribose) polymerase activity study, ethidium bromide/acridine orange differential staining, and transmission, as well as scanning electron microscopic evaluation of ultrastructural changes in microfilariae. Results: The study demonstrates that nanoparticles of silver, but not of gold, elicited significant loss in microfilarial motility. Differential staining of parasites with ethidium bromide and acridine orange, poly(adenosine diphosphate-ribose) polymerase activity in microfilarial lysate, and electron microscopic findings underscored apoptotic death of parasites attributable to nanosilver. In a trypan blue exclusion test, the 50% lethal dose of nanosilver was measured to be 101.2 µM, which was higher than the recorded complete inhibitory concentration value (50.6 µM), thus supporting nanosilver as a potential drug candidate against lymphatic filariasis. Conclusion:The present report provides the first ever conclusive proof in support of apoptosis as a novel stratagem in antifilarial drug designing and nanoscale silver as a valid lead in research on antifilarial therapeutics. The main embargo about the current drug diethylcarbamazine citrate is its empirical use without rationale. Effective microfilaricidal activity of nanosilver at relatively low concentrations as reported in this study, with evidence of the induction of apoptosis in microfilariae, projects nanosilver as a potential drug adjuvant against lymphatic filariasis. The much higher 50% lethal dose value of nanosilver compared to the complete inhibitory concentration value reported in this study argues in favor of a safe therapeutic window of this agent in its antifilarial efficacy.

Potential applications of inorganic silver nanoparticles (AgNPs) in parasitic diseases

“…The NPs induced a marked reduction in the motility of B. malayi microfilariae and an evident decrease in parasite viability. The ultrastructural study and the differential staining assays revealed apoptotic death of parasites under the effect of such NPs, thus supporting their potential as a drug candidate against lymphatic filariasis [96] .…”

Amino Acid-Based Polymer-Coated Silver Nanoparticles as Insulin Fibril Inhibitors

“…The hemolytic percentages of Ag NPs, PAla-AgNPs , PLeu-AgNPs , and PPhe-AgNPs were found to be 3.2, 2.3, 1.4, and 0.8%, respectively. If the hemolytic percentage is less than 5%, samples are regarded as nonhemolytic, according to ISO/TR 7405-1984­(f). , Samples with 5–10% hemolytic percentage are considered to be slightly hemolytic, whereas greater than 10% hemolytic value is considered to be very hemolytic. In our cases, all of the PC-AgNPs showed a hemolytic percentage less than 5% (Figure S9), demonstrating that the NPs are nonhemolytic.…”

Programmed cell death pathways as targets for developing antifilarial drugs: Lessons from the recent findings

“…D‐glucose and hydrazine composite silver nanoparticle is also a very potent filaricid in generating oxidative attack at a very low dose 166 . Report of propidium iodide staining in the degradation of nuclear DNA supports the apoptotic nature of polyvinyl capped silver nanoparticles when treated against S. cervi 167 .…”