Kuznetsova_2025_Chem.Biol.Interact__111678

The search for new systems for drug delivery to the brain is stimulated by the low ability of medicines to overcome the blood-brain barrier (BBB). Liposomes modified with cationic surfactants are promising systems from this point of view. Therefore, new cationic lipid-like surfactants with hexadecyl hydrocarbon tail and different head group structures were synthesized for modification of phosphatidylcholine-based liposomes. To obtain the optimal composition, the surfactant/lipid molar ratio was varied. Modified vesicular nanocontainers were used to load the acetylcholinesterase reactivator, pralidoxime chloride (2-PAM). The physicochemical parameters (hydrodynamic diameter, zeta potential, polydispersity index, aggregate morphology), substrate release profile in vitro, hemolytic activity and hemagglutination ability, as well as 2-PAM pharmacokinetics and AChE reactivation in vivo were examined. The optimized liposomal formulations demonstrated long-term stability. Subsequent evaluation of BBB penetration, 2-PAM pharmacokinetic profile, and in vivo AChE reactivation revealed that the top-performing systems achieved notable brain uptake and reactivated rat brain AChE by 25-38%.