Abstract
It was essential to rapidly reactivate and restore the function of the inhibited acetylcholinesterase(AChE) in the treatment of nerve agents poisoning. However, the blood-brain barrier (BBB) restricts the rapid transport of reactivators from the blood into the brain in therapeutically relevant concentrations. In this study, human serum albumin nanoparticles(HSA NPs) were prepared via desolvent method; HI-6, the known reactivator with higher reactivating efficiency were bound to HSA NPs through electrostatic interaction; at last, on zebrafish BBB model and soman-intoxicated mice, the permeability on BBB and the reactivation on inhibited brain AChE of nanoparticulate oxime formulations were evaluated. All characterization data revealed that HSA NPs loaded with HI-6 had met the basic demand for nanodrug therapy. Compared with free HI-6, HSA NPs loaded HI-6 could cross the BBB and improve the reactivating rates two times, suggesting HSA NPs could carry HI-6 into CNS successfully. In brief, we improved and established a method to prepare the brain-targeted nanoparticles with small-size, low-toxicity and high-efficiency, the targeted drug based on this method could efficiently release and rapidly antagonize the nerve agents poisoning.
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