Globular chitosan prolongs the effective duration time and decreases the acute toxicity of botulinum neurotoxin after intramuscular injection in rats

被引：6

作者：

Sergeevichev, David S. ^{[1
]}

Krasilnikova, Anna A. ^{[1
]}

Strelnikov, Artem G. ^{[1
]}

Fomenko, Vladislav V. ^{[1
,2
]}

Salakhutdinov, Nariman F. ^{[1
,2
]}

Romanov, Alexander B. ^{[1
]}

Karaskov, Alexander M. ^{[1
]}

Pokushalov, Evgeny A. ^{[1
]}

Steinberg, Jonathan S. ^{[3
]}

机构：

[1] Minist Hlth Russian Federat, E Meshalkin Natl Med Res Ctr, Novosibirsk, Russia

[2] Vorozhtsov Inst Organ Chem SB RAS, Novosibirsk, Russia

[3] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA

来源：

TOXICON | 2018年 / 143卷

关键词：

Botulinum toxin A1; Chitosan; Glycosaminoglycans; Threshold stimulation intensity; Block of neuromuscular transmission; TOXIN TYPE-A; CLINICAL-APPLICATIONS; ANTIBODY PROLONGS; MUSCLE STRENGTH; CEREBRAL-PALSY; BIOPOLYMER; COMPLEXES; CHILDREN; EFFICACY; DELIVERY;

D O I：

10.1016/j.toxicon.2018.01.013

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 (LD50) 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. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：90 / 95

页数：6

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