Enhancement of naringenin bioavailability by complexation with hydroxypropyl-β-cyclodextrin. [corrected]

Area of Science:

• Pharmacology
• Drug Delivery
• Biochemistry

Background:

• Naringenin, a flavonoid, exhibits hypolipidemic, anti-inflammatory, and antiviral (HCV) properties.
• Naringenin's clinical utility is limited by poor oral bioavailability.
• Cyclodextrin complexation is a strategy to enhance drug solubility and absorption.

Purpose of the Study:

• To enhance the oral delivery and therapeutic efficacy of naringenin.
• To investigate the effect of hydroxypropyl-β-cyclodextrin (HPβCD) complexation on naringenin's properties.
• To evaluate the in vivo efficacy of naringenin-HPβCD complex in animal models.

Main Methods:

• Complexation of naringenin with HPβCD to improve solubility.
• Assessment of solubility and intestinal permeability using Caco-2 cell models.
• Pharmacokinetic studies in rats to determine plasma concentrations (AUC, Cmax).
• Evaluation of metabolic effects (VLDL, glucose clearance) and molecular targets (PGC1α) in vivo.

Main Results:

• HPβCD increased naringenin solubility by over 400-fold and intestinal transport by 11-fold.
• Naringenin-HPβCD complex showed a 7.4-fold increase in AUC and 14.6-fold increase in Cmax in rats.
• Oral administration of the complex reduced VLDL by 42% and enhanced glucose clearance by 64%.
• Therapeutic effects correlated with increased PGC1α expression in liver and muscle, with no observed toxicity.

Conclusions:

• HPβCD complexation is a promising strategy for enhancing naringenin's oral bioavailability.
• The naringenin-HPβCD complex demonstrates significant potential for treating dyslipidemia, diabetes, and HCV infection.
• This approach offers a viable route for developing naringenin as an oral therapeutic agent.