Abstract
This review is devoted to the medical application of tetrodotoxin (TTX), a potent non-protein specific blocker of voltage-gated sodium (NaV) channels. The selectivity of action, lack of affinity with the heart muscle NaV channels, and the inability to penetrate the blood–brain barrier make this toxin an attractive candidate for anesthetic and analgesic drug design. The efficacy of TTX was shown in neuropathic, acute and inflammatory pain models. The main emphasis of the review is on studies focused on the improvement of TTX efficacy and safety in conjunction with additional substances and drug delivery systems. A significant improvement in the effectiveness of the toxin was demonstrated when used in tandem with vasoconstrictors, local anesthetics and chemical permeation enhancers, with the best results obtained with the encapsulation of TTX in microparticles and liposomes conjugated to gold nanorods.
Highlights
The medical community defines neurotoxins as substances that damage, destroy or disrupt the function of nervous tissue at low concentrations
The acute and instantaneous effect on the nervous system at concentrations far lower than their median lethal dose (LD50) allows minimal concentrations of neurotoxins to be used to reach the desired effect [1]. Their high toxicity raises a safety issue in relation to the use of neurotoxins and highlights the need for the careful development of the formulation of the drug, which can often be improved by the co-application of other medications and by elaborate systems of drug administration and targeted delivery [2]
This review is devoted to the medical applications of TTX, with a special emphasis on studies focused on the improvement of its efficacy and safety in conjunction with additional substances and drug delivery systems
Summary
The medical community defines neurotoxins as substances that damage, destroy or disrupt the function of nervous tissue at low concentrations. The acute and instantaneous effect on the nervous system at concentrations far lower than their median lethal dose (LD50) allows minimal concentrations of neurotoxins to be used to reach the desired effect [1] Their high toxicity raises a safety issue in relation to the use of neurotoxins and highlights the need for the careful development of the formulation of the drug, which can often be improved by the co-application of other medications and by elaborate systems of drug administration and targeted delivery [2]. Neurotoxins do not just have a long history of application in medical practice, but have initiated new directions in drug design and development In this context, it is worth noting curare, botulinum toxin, and morphine. This review is devoted to the medical applications of TTX, with a special emphasis on studies focused on the improvement of its efficacy and safety in conjunction with additional substances and drug delivery systems
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