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Oxime Therapy for Brain AChE Reactivation and Neuroprotection after Organophosphate Poisoning

Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, Russia
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Academic Editor: Carlotta Marianecci
Pharmaceutics 2022, 14(9), 1950; https://doi.org/10.3390/pharmaceutics14091950
Received: 29 July 2022 / Revised: 31 August 2022 / Accepted: 9 September 2022 / Published: 15 September 2022
(This article belongs to the Special Issue Liposomal and Lipid-Based Drug Delivery Systems and Vaccines)
One of the main problems in the treatment of poisoning with organophosphorus (OPs) inhibitors of acetylcholinesterase (AChE) is low ability of existing reactivators of AChE that are used as antidotes to cross the blood-brain barrier (BBB). In this work, modified cationic liposomes were developed that can penetrate through the BBB and deliver the reactivator of AChE pralidoxime chloride (2-PAM) into the brain. Liposomes were obtained on the basis of phosphatidylcholine and imidazolium surfactants. To obtain the composition optimized in terms of charge, stability, and toxicity, the molar ratio of surfactant/lipid was varied. For the systems, physicochemical parameters, release profiles of the substrates (rhodamine B, 2-PAM), hemolytic activity and ability to cause hemagglutination were evaluated. Screening of liposome penetration through the BBB, analysis of 2-PAM pharmacokinetics, and in vivo AChE reactivation showed that modified liposomes readily pass into the brain and reactivate brain AChE in rats poisoned with paraoxon (POX) by 25%. For the first time, an assessment was made of the ability of imidazolium liposomes loaded with 2-PAM to reduce the death of neurons in the brains of mice. It was shown that intravenous administration of liposomal 2-PAM can significantly reduce POX-induced neuronal death in the hippocampus. View Full-Text
Keywords: cationic liposome; imidazolium surfactant; targeted drug delivery; acetylcholinesterase reactivation; blood-brain barrier cationic liposome; imidazolium surfactant; targeted drug delivery; acetylcholinesterase reactivation; blood-brain barrier
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MDPI and ACS Style

Kuznetsova, D.A.; Gaynanova, G.A.; Vasilieva, E.A.; Pavlov, R.V.; Zueva, I.V.; Babaev, V.M.; Kuznetsov, D.M.; Voloshina, A.D.; Petrov, K.A.; Zakharova, L.Y.; Sinyashin, O.G. Oxime Therapy for Brain AChE Reactivation and Neuroprotection after Organophosphate Poisoning. Pharmaceutics 2022, 14, 1950. https://doi.org/10.3390/pharmaceutics14091950

AMA Style

Kuznetsova DA, Gaynanova GA, Vasilieva EA, Pavlov RV, Zueva IV, Babaev VM, Kuznetsov DM, Voloshina AD, Petrov KA, Zakharova LY, Sinyashin OG. Oxime Therapy for Brain AChE Reactivation and Neuroprotection after Organophosphate Poisoning. Pharmaceutics. 2022; 14(9):1950. https://doi.org/10.3390/pharmaceutics14091950

Chicago/Turabian Style

Kuznetsova, Darya A., Gulnara A. Gaynanova, Elmira A. Vasilieva, Rais V. Pavlov, Irina V. Zueva, Vasily M. Babaev, Denis M. Kuznetsov, Alexandra D. Voloshina, Konstantin A. Petrov, Lucia Y. Zakharova, and Oleg G. Sinyashin. 2022. "Oxime Therapy for Brain AChE Reactivation and Neuroprotection after Organophosphate Poisoning" Pharmaceutics 14, no. 9: 1950. https://doi.org/10.3390/pharmaceutics14091950

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