A novel supramolecular nanodrugs for improving the cognitive function of schizophrenia by protecting active lactone of arecoline.

Abstract

Over 30 % of patients with schizophrenia experience treatment resistance and severe side effects. The limited efficacy of antipsychotic therapies poses a challenge, partly due to the blood-brain barrier (BBB) and the non-selective targeting of these drugs. Herein, we report on arecoline (ARE), a water soluble natural small molecule, which was successfully constructed a phospholipid complex by noncovalent interactions. Most striking, this arecoline-phospholipid complex nanoplatforms (ARE-PC NPs) could prevent the hydrolyzation of its ester group by carboxylesterases, which showed sustained release, superior physiological stability and long circulatory capability. Both in vitro cells and in vivo mice speculated that this ARE-PC NPs might has a high cellular uptake and stronger penetration ability of the BBB. Additionally, our results demonstrated that this phospholipid complex might facilitate ARE delivery to the brain tissue and obviously improve the schizophrenia-like behavior in cuprizone induced animal models. This study highlights ARE-PC NPs as a promising antipsychotic nanodrug for the therapy of schizophrenia.