Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

Area of Science:

• Pharmacology
• Materials Science
• Biochemistry

Background:

• Chrysin, a natural bioflavonoid, exhibits antioxidant, anti-inflammatory, and anti-cancer properties.
• Poor water solubility and limited bioavailability hinder chrysin's therapeutic applications.
• Developing effective delivery systems is crucial for maximizing chrysin's potential.

Purpose of the Study:

• To evaluate the solubilization capacity of various beta-cyclodextrin derivatives for chrysin.
• To compare the biological activities and absorption enhancement of chrysin-cyclodextrin complexes.
• To identify the optimal cyclodextrin for improving chrysin's physicochemical and pharmacokinetic properties.

Main Methods:

• Chrysin was complexed with beta-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPBCD), sulfobutylether-β-cyclodextrin (SBECD), and randomly-methylated-β-cyclodextrin (RAMEB) using lyophilization.
• Solubility, phase solubility, cytotoxicity (MTT assay), and Caco-2 monolayer permeability were assessed.
• Complexes were prepared in 1:1 and 1:2 molar ratios.

Main Results:

• RAMEB demonstrated the highest water solubility for chrysin complexes.
• Phase solubility studies indicated the strongest interaction between RAMEB and chrysin.
• RAMEB complexes significantly enhanced chrysin permeability across Caco-2 monolayers without exhibiting cytotoxicity.
• No cytotoxicity was observed for any complex up to 100 µM.

Conclusions:

• Beta-cyclodextrin derivatives, particularly RAMEB, are effective in improving chrysin's aqueous solubility.
• RAMEB significantly enhances chrysin's intestinal absorption and permeability.
• These findings suggest RAMEB as a promising carrier for improving chrysin bioavailability and therapeutic efficacy.