Encapsulation of oxime K027 into cucurbit[7]uril: In vivo evaluation of safety, absorption, brain distribution and reactivation effectiveness

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F20%3A50016692" target="_blank" >RIV/62690094:18470/20:50016692 - isvavai.cz</a>

Alternative codes found

RIV/60162694:G44__/20:00555463 RIV/00179906:_____/20:10410996

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0378427419303789?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378427419303789?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.toxlet.2019.11.021" target="_blank" >10.1016/j.toxlet.2019.11.021</a>

Result language

angličtina

Original language name

Encapsulation of oxime K027 into cucurbit[7]uril: In vivo evaluation of safety, absorption, brain distribution and reactivation effectiveness

Original language description

Oxime-based acetylcholinesterase reactivators (briefly oximes) regenerate organophosphate-inactivated acetylcholinesterase and restore its function. Poor blood-brain-barrier passage and fast elimination from blood limit their actual use in treatment of patients exposed to organophosphates. Previous in vitro results implicated further testing of cucurbit[7]uril as a delivery vehicle for bisquaternary oximes. The present paper focuses on cell toxicity, in vivo safety and influence of cucurbit[7]uril on oxime pharmacokinetics and pharmacodynamics. Neither the K027 nor the complex caused any cell toxicity, changes in blood biochemistry or hepato- or nephrotoxicity in tested concentrations. The encapsulation of K027 increased and accelerated the blood-brain-barrier penetration. The peripheral oxime exposure also increased, supporting the suggestion that cucurbit[7] uril protects the circulating oxime from rapid renal clearance. Contrary to the comparable in vitro reactivation power of K027 and the encapsulated K027, we failed to confirm this in vivo. In theory, this might result from the non-specific binding of molecules to the cucurbit[7]uril or the interaction of K027 with cucurbit[7]uril being too strong for acetylcholinesterase reactivation. Precise explanation requires additional in silico, in vitro and also in vivo experiments.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30108 - Toxicology

Project

<a href="/en/project/GA18-08937S" target="_blank" >GA18-08937S: Research of oxime-CB(7) complexes for central nervous system penetration of quaternary acetylcholinesterase reactivator</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Toxicology letters

ISSN

0378-4274

e-ISSN

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Volume of the periodical

320

Issue of the periodical within the volume

March

Country of publishing house

IE - IRELAND

Number of pages

9

Pages from-to

64-72

UT code for WoS article

000505022400009

EID of the result in the Scopus database

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