title: Novel microfilaricidal activity of nanosilver.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Singh
authors.forename: Kalyan
authors.initials: K
authors.lastname: Goswami
authors.forename: Richa D
authors.initials: RD
authors.lastname: Sharma
authors.forename: Maryada V R
authors.initials: MV
authors.lastname: Reddy
authors.forename: Debabrata
authors.initials: D
authors.lastname: Dash
mesh_terms: D000165:Acridine Orange / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017178:Brugia malayi / Q000187:drug effects*; D004996:Ethidium / Q000737:chemistry; D005368:Filariasis / Q000469:parasitology; D005369:Filaricides / Q000737:chemistry / Q000494:pharmacology*; D005849:Gerbillinae; D006046:Gold / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015203:Reproducibility of Results; D012834:Silver / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D005369:Filaricides; D012834:Silver; D006046:Gold; D011065:Poly(ADP-ribose) Polymerases; D004996:Ethidium; D000165:Acridine Orange