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A novel simple protocol for the layer-by-layer coating of uncharged organic substrates (hydrophobic carboxylic acid esters, CAEs) and control of their loading/release behavior has been developed. The approach involves the preliminary treatment of CAEs with the cationic surfactant cetyltrimethylammonium bromide followed by poly(acrylic acid)/polyethyleneimine alternate deposition. The basic hydrolysis of the substrates is used to spectrophotometrically control the loading/release behavior through monitoring the absorbency of the reaction product p-nitrophenolate ion. Unlike the reactivity of free CAEs, highly sensitive to the solution pH, and the presence of micellar catalysts, the reaction rate of the loaded substrates is unaffected by reaction conditions and can be administered by the capsule design (numbers of deposition cycles, adjusted pH, ultrasonication). The developed protocol makes it possible to omit the use of the sacrificial template and stages of its removal. Capsules corresponding to the biorelevant size criterion, with diameter of ≤200 nm, are obtained. They can be successfully applied for sustaining the dosage of different specimens with the desirable rate and for the control of the guest reactivity by tuning the shell permeability.

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.