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Study finds nanosilver as a potential drug candidate against lymphatic filariasis

New Delhi: A joint study conducted by researchers at the biochemistry departments of Institute of Medical Sciences, Banaras Hindu University (BHU), Varanasi, and Mahatma Gandhi Institute of Medical Sciences, Sevagram shows that nanoparticles of silver (10-15 nm diameter) have potent microfilaricidal effect against Brugia malayi in vitro.

Dr Debabrata Dash

“Although nanoscale silver is well known to have antibacterial effect, it is the first demonstration of their anti-parasitic efficacy,” says study author Dr Debabrata Dash, professor and head, department of biochemistry, Institute of Medical Sciences, BHU. “Thus nanosilver may be a supplement to the conventional anti-filarial drug diethylcarbamazine citrate (DEC).”

Other authors on the paper include Sunil K Singh of the department of biochemistry, Institute of Medical Sciences, BHU and Kalyan Goswami, Richa D Sharma and Maryada VR Reddy of the department of biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram.

The study findings have been published in the International Journal of Nanomedicine.

Human lymphatic filariasis is a major vector-borne disease in countries of tropical and subtropical regions. It is caused by the nematode parasites Wuchereria bancrofti and Brugia malayi. The adult forms of the parasites harbour in host lymphatic tissue, whereas the microfilarial forms (Mf) circulate in the blood as a reproductive product. The latter are transmitted to the mosquito vector where the larval (infective) stage is generated. Passage of infective larvae into humans and subsequent development into adult worms complete the life cycle.

According to the Indian Council of Medical Research (ICMR), more than 550 million people are exposed to filarial infection in India, which is estimated to be 40 per cent of the total global burden of the disease.

For the last century, DEC has been almost the sole antifilarial drug, and its inherent disadvantages such as unwanted side effects, lack of patient compliance, and poor macrofilaricidal effectiveness have warranted research on new antifilarial drug development.

Nanoparticles of silver (AgNPs) 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.

During the study, the researchers analysed 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 researchers found that nanoparticles of silver, but not of gold, elicited significant loss in microfilarial motility. This study did not find any serious toxicity concern with silver.

Nanosilver may act synergistically with DEC and thus may be effective either individually or as an adjunct (at lower individual doses) to this standard drug, after critical evaluation of safety parameters. Although there have been concerns regarding the toxicity of nanoparticles in general, and silver in particular, nanosilver might be considered to have a safe therapeutic window. The 50 per cent lethal dose of nanosilver (100 ?M), which is double the complete inhibitory concentration value (50 ?M) as reported in the present study, supports this contention.

“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,” say the researchers.

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