Effective and Stable Senomorphic Apigenin Delivery System Obtained by Supercritical Carbon Dioxide Processing

Area of Science:

• Pharmacology and Pharmaceutical Sciences
• Materials Science
• Biochemistry

Background:

• Apigenin (AP), a natural flavonoid, possesses senomorphic and neuroprotective properties.
• Poor aqueous solubility of AP (<1 μg/mL) severely limits its bioavailability and therapeutic applications.
• Developing strategies to enhance AP solubility is crucial for its effective utilization.

Purpose of the Study:

• To create a stable amorphous dispersion of apigenin (AP) using supercritical carbon dioxide (scCO2) processing.
• To evaluate the enhanced solubility, bioavailability, and biological activities of the AP amorphous dispersion.
• To confirm the stability and characterize the intermolecular interactions within the AP dispersion.

Main Methods:

• Screening of AP solubilization with Soluplus (SOL) under scCO2 conditions.
• Optimization of scCO2 processing parameters (temperature, pressure) for maximum AP solubility.
• Characterization using X-ray powder diffraction (XRPD), PAMPA model, ATR-FT-IR, and chromatographic analysis.
• Assessment of antioxidant (DPPH, ABTS, CUPRAC) and anticholinesterase (AChE, BChE) activities.

Main Results:

• Soluplus significantly improved AP dissolution, reaching 8050.2 ± 35.1 μg/mL under optimized scCO2 conditions.
• XRPD confirmed amorphization, leading to enhanced AP dissolution across acidic and neutral pH.
• Improved membrane penetration (gastrointestinal and blood-brain barriers) and 12-month stability of the amorphous dispersion.
• Enhanced antioxidant and neuroprotective activities (anticholinesterase inhibition) correlated with improved solubility.

Conclusions:

• A stable amorphous AP dispersion was successfully prepared using scCO2 and Soluplus, exhibiting excellent solubility and stability.
• The developed formulation demonstrates enhanced passive diffusion across biological membranes.
• The improved AP dispersion offers greater potential for effective antioxidant and neuroprotective therapies.