New research has found a toxin extracted from the venom of a South American rattlesnake can function as an effective analgesic for neuropathic pain. The Brazilian study reveals the venom’s toxicity can be reduced by encapsulating it in tiny silica particles, with early animal studies delivering promising results.
Crotoxin is the main neurotoxin found in venom of the South American rattlesnake Crotalus durissus terrificus. The toxin's therapeutic potential has been well studied by scientists for decades, from an impressive anti-inflammatory effect to its compelling anti-cancer potential.
"I've been studying crotoxin since 2011,” says Gisele Picolo, one of the researchers working on the new study. “The results are positive in terms of its analgesic effect, but its toxicity has always been a constraint.”
Finding a way to reduce the harmful toxicity of crotoxin while maintaining, or even enhancing, its therapeutic effect has been a challenge for researchers. A potential solution to the research hurdle came when a separate team of vaccine scientists began reporting the results of testing a new way of administering vaccines.
The goal of an effective vaccine is to stimulate the body’s natural immune response. Osvaldo Sant'Anna is a researcher working on encapsulating vaccine antigens within tiny particles of mesoporous silica. His work has found when antigens are administered in mesoporous silica particles mice produce more antibodies resulting in a more efficacious vaccine.
But, other tests using toxins with the silica resulted in interesting protective effects, essentially reducing the potency of a toxin.
"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," says Osvaldo Sant'Anna.
These findings led Picolo and her colleagues to explore whether these mesoporous silica particles could be an effective way at delivering crotoxin. The first animal tests revealed the crotoxin/silica formulation was indeed less toxic than crotoxin administered alone. In fact, the researchers were able to deliver 35 percent higher doses of crotoxin when encapsulated in the silica particles.
Subsequent experiments found that not only was the new crotoxin formulation effective at reducing acute and chronic neuropathic pain, but its total analgesic duration was extended when administrated with the silica. The formulation reduced pain sensitivity for up to 48 hours following just one dose. The novel honeycomb-like structure of the silica particles also prevented the crotoxin from being broken down in the stomach, allowing for oral administration.
"It also guarantees controlled release of the crotoxin in the organism, which may explain the lasting analgesic effect," says Picolo.
Despite these promising results, the research is still in its earliest stages. No results of human tests have been published so far, however, even if the novel formulation proves safe and effective in clinical trials there are other hurdles to overcome before the treatment becomes available.
At this point scientists have not found a method to easily synthesize the toxin, meaning it can only be obtained directly from rattlesnake venom, and obviously this could not easily shift into the mass production necessary for a new widely distributed painkiller.
"Crotoxin is a large molecule with a complex structure that's hard to replicate in the laboratory, so scaled-up use is a long away off," adds Picolo.
The new research was published in the journal Toxins.
Source: Agencia FAPESP
