Current approaches to enhancing oxime reactivator delivery into the brain

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F19%3A00536978" target="_blank" >RIV/60162694:G44__/19:00536978 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/19:10400302

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0300483X19301581" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0300483X19301581</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tox.2019.05.006" target="_blank" >10.1016/j.tox.2019.05.006</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Current approaches to enhancing oxime reactivator delivery into the brain

Popis výsledku v původním jazyce

The misuse of organophosphate compounds still represents a current threat worldwide. Treatment of poisoning with organophosphates (OPs) remains unsatisfactorily resolved despite the extensive investment in research in academia. There are no universal, effective and centrally-active acetylcholinesterase (AChE) reactivators to countermeasure OP intoxication. One major obstacle is to overcome the blood-brain barrier (BBB). The central compartment is readily accessible by the OPs which are lipophilic bullets that can easily cross the BBB, whereas first-line therapeutics, namely oxime-based AChE reactivators and atropine, do not cross or do so rather slowly. The limitation of oxime-based AChE reactivators can be ascribed to their chemical nature, bearing a positive charge which is essential either for their AChE affinity or their reactivating potency. The aim of this article is to review the methods for targeting the brain by oxime reactivators that have been developed so far. Approaches using prodrugs, lipophilicity enhancement, or sugar-based oximes have been rather unsuccessful. However, other strategies have been more promising, such as the use of nanoparticles or co-administration of the reactivator with efflux transporter inhibitors. Encouraging results have also been associated with intranasal delivery, but research in this field is still at the beginning. Further research of auspicious approaches is inevitable

Název v anglickém jazyce

Current approaches to enhancing oxime reactivator delivery into the brain

Popis výsledku anglicky

The misuse of organophosphate compounds still represents a current threat worldwide. Treatment of poisoning with organophosphates (OPs) remains unsatisfactorily resolved despite the extensive investment in research in academia. There are no universal, effective and centrally-active acetylcholinesterase (AChE) reactivators to countermeasure OP intoxication. One major obstacle is to overcome the blood-brain barrier (BBB). The central compartment is readily accessible by the OPs which are lipophilic bullets that can easily cross the BBB, whereas first-line therapeutics, namely oxime-based AChE reactivators and atropine, do not cross or do so rather slowly. The limitation of oxime-based AChE reactivators can be ascribed to their chemical nature, bearing a positive charge which is essential either for their AChE affinity or their reactivating potency. The aim of this article is to review the methods for targeting the brain by oxime reactivators that have been developed so far. Approaches using prodrugs, lipophilicity enhancement, or sugar-based oximes have been rather unsuccessful. However, other strategies have been more promising, such as the use of nanoparticles or co-administration of the reactivator with efflux transporter inhibitors. Encouraging results have also been associated with intranasal delivery, but research in this field is still at the beginning. Further research of auspicious approaches is inevitable

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/NV17-32801A" target="_blank" >NV17-32801A: Centrálně účinná antidota pro léčbu otrav organofosfáty</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Toxicology

ISSN

0300-483X

e-ISSN

0300-483X

Svazek periodika

423

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

9

Strana od-do

75-83

Kód UT WoS článku

000483417200006

EID výsledku v databázi Scopus

2-s2.0-85066068619