Chrysin-phospholipid complex-based solid dispersion for improved anti-aging and neuroprotective effects in mice

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 beta cyclodextrin (2-HP beta CD) and polyvinylpyrrolidone 8000. CHR-PLC/2-HP beta CD (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-HP beta CD 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 PGC1 alpha brain contents as well as a reduction of AGEs, GFAP, NT-3, TNF-alpha, and NF-kappa beta 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.