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

Area of Science:

• Pharmacology
• Neuroscience
• Materials Science

Background:

• Chrysin (CHR) exhibits neuroprotective potential but suffers from poor solubility and bioavailability.
• Developing advanced drug delivery systems is crucial for enhancing CHR's therapeutic efficacy.
• Phospholipid complexation and solid dispersion are promising techniques for improving drug delivery.

Purpose of the Study:

• To enhance the neuroprotective effects of chrysin (CHR) by developing novel formulations.
• To combine phospholipid complexation and solid dispersion techniques for improved chrysin delivery.
• To evaluate the efficacy of these advanced formulations in a mouse model of brain aging.

Main Methods:

• Prepared chrysin-phospholipid complex (CHR-PLC) via solvent evaporation.
• Developed solid dispersions (SD) of CHR-PLC using 2-hydroxypropyl β cyclodextrin (2-HPβCD) and polyvinylpyrrolidone 8000.
• Assessed in vitro solubility and dissolution profiles, and in vivo neuroprotective effects in D-galactose induced brain aging mice.

Main Results:

• The optimized CHR-PLC loaded solid dispersion (CHR-PLC-SD4) showed a 5.86-fold increase in aqueous solubility and a six-fold enhancement in dissolution rate compared to plain chrysin.
• In vivo studies demonstrated significant improvements in behavioral activity, elevated levels of neurogenesis and mitochondrial biogenesis markers (AMPK, LKB1, PGC1α), and reduced markers of neuroinflammation and degeneration (AGEs, GFAP, NT-3, TNF-α, NF-κβ).
• The formulation CHR-PLC-SD4 exhibited superior neuroprotective activity compared to CHR-PLC, CHR-SD, and plain chrysin.

Conclusions:

• The combined phospholipid complexation and solid dispersion approach effectively enhanced chrysin's solubility, dissolution, and neuroprotective efficacy.
• The developed CHR-PLC-SD formulation shows significant potential for treating brain aging by stimulating neurogenesis and mitochondrial biogenesis while suppressing neuroinflammation and neurodegeneration.
• This study highlights a promising strategy for improving the therapeutic application of poorly soluble natural compounds like chrysin.