Novel formulation allows use of toxin from rattlesnake venom to control neuropathic pain

Novel formulation allows use of toxin from rattlesnake venom to control neuropathic pain

Crotoxin, extracted from the venom of the South American rattlesnake Crotalus durissus terrificus, has been studied for almost a century for its analgesic, anti-inflammatory and antitumor activities and as an even more powerful muscle paralyzer than botulinum toxin. However, the toxicity of crotoxin limits its medicinal use. A new study, published by Brazilian researchers in the journal Toxins , shows that crotoxin's therapeutic effects can be enhanced and its toxicity reduced when it is encapsulated in nanostructured SBA-15 silica, a material originally developed for use in vaccine formulations. The study was conducted under the aegis of Brazil's National Science and Technology Institute (INCT) on Toxins , one of the INCTs supported by FAPESP (São Paulo Research Foundation) in São Paulo State in partnership with the National Council for Scientific and Technological Development (CNPq), an agency of the Brazilian government. The INCT's principal investigator is Osvaldo Augusto Sant'Anna. The study was part of the doctoral research of Morena Brazil Sant'Anna, whose thesis advisor is Gisele Picolo. Picolo herself was the principal investigator for a project on the same topic. Researchers Flavia Souza Ribeiro Lopes and Louise Faggionato Kimura participated in the study, which was performed at Butantan Institute in São Paulo. Osvaldo Sant'Anna is the principal investigator for a Thematic Project at Butantan Institute to study mesoporous silica as a vaccine adjuvant in collaboration with Márcia Fantini, a professor at the University of São Paulo's Physics Institute (IF-USP). An adjuvant is an agent used in conjunction with a vaccine antigen to augment the host's antigen-specific immune response. "People who respond badly to vaccines usually have macrophages that catabolize the antigen very quickly, so there isn't time for their lymphocytes to induce a complete response in terms of producing antibodies," Osvaldo Sant'Anna told Agência FAPESP. "Research has shown that nanostructured silica slows the macrophages down." Osvaldo Sant'Anna's studies show that mice produce more antibodies against an antigen when it is administered with silica, which is made up of microstructures and can be molded to encapsulate molecules of varying shapes and sizes. When silica was tested with other toxins, a novel protective effect was discovered. "In tests conducted in horses to produce anti-diphtheria serum and with tetanus toxin, we found that silica makes antigens less potent and reduces the adverse effect of diphtheria toxin," Osvaldo Sant'Anna said. These findings were welcomed by Picolo and Morena Brazil Sant'Anna, colleagues of Osvaldo Sant'Anna at Butantan Institute. "I've been studying crotoxin since 2011. The results are positive in terms of its analgesic effect, but its toxicity has always been a constraint. Using silica was a great idea. This is the first time the two molecules have been combined," Picolo said. Neuropathic pain The article published in Toxins reports on a study designed to investigate the effects of crotoxin combined with SBA-15 silica when used to treat neuropathic pain, a chronic condition caused by injuries to sensitized nerves. Treating chronic pain is a challenge for physicians because ordinary painkillers such as anti-inflammatory drugs and opioids do not have the desired effect. To evaluate crotoxin's therapeutic potential in this setting, the researchers conducted experiments with mice, inducing a condition similar to neuropathic pain by injuring the sciatic nerve. The first positive finding resulted from a test to determine the maximum dose of crotoxin with and without silica. "We observed that a larger amount of the toxin combined with silica could be administered without adverse side effects and that the dose could therefore be increased," Morena Brazil Sant'Anna said. It was possible to administer a 35% larger dose of crotoxin when it was combined with silica. Related Stories



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