LAUSR

Abstract The present study aimed to improve the neuroprotective effect of chrysin (CHR) by combining two formulation techniques, phospholipid (PL) complexation and solid dispersion (SD). CHR-phospholipid complex (CHR-PLC) was prepared through solvent evaporation. The molar ratio CHR/PL (1:3), which exhibited the highest complexation efficiency, was selected for the preparation of CHR-PLC loaded SD (CHR-PLC-SD) with 2-hydroxypropyl β cyclodextrin (2-HPβCD) and polyvinylpyrrolidone 8000. CHR-PLC/2-HPβCD (1:2, w/w) displayed the highest aqueous solubility of CHR (5.86 times more than that of plain CHR). CHR-SD was also prepared using 2-HPβCD for comparison. The in vitro dissolution of CHR-PLC-SD4 revealed an enhancement in the dissolution rate over CHR-PLC (1:3), CHR-SD, and plain CHR by six times. The optimum formulations and plain CHR were evaluated for their neuroprotective effect on brain aging induced by D-galactose in mice. The results demonstrated a behavioral activity elevation, an increase of AMPK, LKB1, and PGC1α brain contents as well as a reduction of AGEs, GFAP, NT-3, TNF-α, and NF-κβ brain contents when compared with those of the D-galactose control group. Thus, the developed formulations stimulated neurogenesis and mitochondrial biogenesis as well as suppressed neuroinflammation and neurodegeneration. The order of activity was as follows: CHR-PLC-SD4 > CHR-PLC (1:3) > CHR-SD > plain CHR. Graphical abstract