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.