Novel Supramolecular Nanoparticles Modified with Phosphatidylcholine Improve the Bioavailability of Fisetin and Alleviate Alcoholism through Antioxidant and Antiinflammatory Effects

Abstract

Excessive alcohol consumption frequently induces pathological alterations in various organs. Currently, there is no specific therapeutic drug for the treatment of alcoholism. Fisetin (FIT) is a bioactive dietary polyphenol present in various fruits and vegetables, associated with positive health effects. However, there is still a lack of research on its efficacy in alleviating alcoholism. In addition, its poor water solubility and stability limit its efficacy. This study aims to enhance its stability, biocompatibility, bioavailability, and efficacy in alleviating alcoholism by using kolliphor HS15, plasdone S630, and phosphatidylcholine to prepare novel phosphatidylcholine-modified supramolecular nanoparticles of FIT (FIT-MSN). FIT-MSN exhibited a size of 51.90 ± 0.15 nm, with a polydispersity index of 0.265 ± 0.008. The solubility of FIT-MSN in 37 °C water was increased by >456-fold. Because of its optimal particle size, high stability, excellent water solubility, permeability, biocompatibility, and P-glycoprotein inhibitory effect, FIT-MSN demonstrated substantially enhanced intestinal absorption, resulting in a 9.44-fold increase in the area under the curve_(0–24 h) compared with that of FIT. Furthermore, the experiments demonstrated that phosphatidylcholine-modified nanoparticles exhibit superior absorption, bioavailability, and liver targeting compared to conventional nanoparticles. Animal investigations revealed that FIT-MSN significantly delayed the onset of loss of righting reflex, reduced the blood alcohol content, and increased the activity of alcohol dehydrogenase and aldehyde dehydrogenase (P < 0.05). In addition, FIT-MSN may exhibit antiinflammatory effects via the regulation of the MAPK/NF-κB signaling pathway and exert antioxidant effects through the upregulation of Nrf2 expression, thus mitigating alcohol-induced gastric injury. In short, FIT-MSN not only demonstrated remarkable efficacy in alleviating alcoholism but also proved to be quite safe.