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

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

Journal

Toxicon
ISSN: 0041-0101

Output data

Year: 2018, Volume: 143, Pages: 90-95 Pages count : 6 DOI: 10.1016/j.toxicon.2018.01.013

Tags

Botulinum toxin A1; Chitosan; Glycosaminoglycans; Threshold stimulation intensity; Block of neuromuscular transmission

Authors

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

Affiliations

1	(Данные Web of science) Minist Hlth Russian Federat, E Meshalkin Natl Med Res Ctr, Novosibirsk, Russia
2	(Данные Web of science) Vorozhtsov Inst Organ Chem SB RAS, Novosibirsk, Russia
3	(Данные Web of science) Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA

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.

Sergeevichev D.S. , Krasilnikova A.A. , Strelnikov A.G. , Fomenko V.V. , Salakhutdinov N.F. , Romanov A.B. , Karaskov A.M. , Pokushalov E.A. , Steinberg J.S.
Globular chitosan prolongs the effective duration time and decreases the acute toxicity of botulinum neurotoxin after intramuscular injection in rats
Toxicon. 2018. V.143. P.90-95. DOI: 10.1016/j.toxicon.2018.01.013 WOS Scopus РИНЦ

Published print:

Mar 1, 2018

Web of science	WOS:000426223300011
Scopus	2-s2.0-85041402708
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