Sergeevichev David S, Krasilnikova Anna A, Strelnikov Artem G, Fomenko Vladislav V, Salakhutdinov Nariman F, Romanov Alexander B, Karaskov Alexander M, Pokushalov Evgeny A, Steinberg Jonathan S
"E. Meshalkin National Medical Research Center" of the Ministry of Health of the Russian Federation, Novosibirsk, Russian Federation.
"E. Meshalkin National Medical Research Center" of the Ministry of Health of the Russian Federation, Novosibirsk, Russian Federation.
Toxicon. 2018 Mar 1;143:90-95. doi: 10.1016/j.toxicon.2018.01.013. Epub 2018 Jan 31.
Botulinum neurotoxin (BoNT) is used for an increasing number of neurological and non-neurological indications and disorders. Since the duration of action of this neurotoxin is limited, the goal of the work was to improve the pharmacological time course of BoNT. We explored the effect of several polysaccharides on the duration of action of BoNT/A1 in rat electromyography. The formulation of BoNT/A1 containing globular chitosan increased the threshold stimulation intensity almost 2 times in 30 days after injection if compared with the baseline threshold. However, conventional linear chitosan, heparin and hyaluronic acid did not have such an effect. In addition, we compared the effectiveness of different doses of BoNT/A1 (25, 50, 75, and 100 U) with globular chitosan and compared the acute toxicity of this formulation with that of BoNT/A1 in physiological saline after intramuscular injection. The results demonstrated that the dose 25 U of BoNT/A1 with globular chitosan was both effective and safe for animals after intramuscular injection. The assessed median lethal dose (LD) for intramuscular injection in rats was 1.4 times higher for a combination of BoNT/A1 with globular chitosan than that for a solution of BoNT/A1 in physiological saline. Thus, the results of our study have provided evidence that intramuscular injection of the formulation of BoNT/A1 (25 U) containing globular chitosan in rats is safe and significantly prolongs the effective duration time of BoNT/A1.
肉毒杆菌神经毒素（BoNT）被用于越来越多的神经和非神经适应症及病症。由于这种神经毒素的作用持续时间有限，该研究的目标是改善BoNT的药理学时间进程。我们探究了几种多糖对大鼠肌电图中BoNT/A1作用持续时间的影响。与基线阈值相比，注射含球状壳聚糖的BoNT/A1制剂在30天后可使阈刺激强度增加近2倍。然而，传统的线性壳聚糖、肝素和透明质酸并无此效果。此外，我们比较了不同剂量（25、50、75和100单位）的BoNT/A1与球状壳聚糖的有效性，并比较了该制剂与肌肉注射生理盐水后BoNT/A1的急性毒性。结果表明，肌肉注射后，25单位的BoNT/A1与球状壳聚糖对动物既有效又安全。大鼠肌肉注射的评估半数致死剂量（LD）显示，BoNT/A1与球状壳聚糖的组合比BoNT/A1生理盐水溶液高1.4倍。因此，我们的研究结果证明，在大鼠中肌肉注射含球状壳聚糖的BoNT/A1（25单位）制剂是安全的，且能显著延长BoNT/A1的有效持续时间。
