Enhancing hepatoprotective action: oxyberberine amorphous solid dispersion system targeting TLR4.

Area of Science:

• Pharmacology
• Drug Delivery
• Natural Products Chemistry

Background:

• Oxyberberine (OBB) possesses notable hepatoprotective properties.
• Poor water solubility of OBB limits its bioavailability and therapeutic efficacy.
• Developing advanced formulations is crucial for enhancing OBB's pharmaceutical potential.

Purpose of the Study:

• To formulate amorphous spray-dried powders (ASDs) of OBB to improve its solubility and bioavailability.
• To investigate the characterization, dissolution, and pharmacokinetic profiles of OBB-ASDs.
• To evaluate the hepatoprotective efficacy of OBB-ASDs in a D-GalN/LPS-induced acute liver injury (ALI) mouse model.

Main Methods:

• Formulation of OBB-ASDs using spray-drying technology.
• Characterization of OBB-ASDs to confirm the amorphous state of OBB.
• In vitro dissolution studies and in vivo pharmacokinetic assessments.
• Induction of ALI in mice using D-GalN/LPS and subsequent treatment with OBB-ASDs.

Main Results:

• Spray drying successfully converted crystalline OBB into an amorphous form within OBB-ASDs.
• OBB-ASDs exhibited significantly enhanced bioavailability compared to OBB active pharmaceutical ingredients (API).
• OBB-ASDs treatment ameliorated liver histopathology, improved liver function, and reduced inflammation and oxidative stress in ALI mice.

Conclusions:

• Spray drying is an effective method for producing amorphous OBB, enhancing its bioavailability and hepatoprotective activity.
• OBB-ASDs demonstrate significant potential as a drug delivery system for treating acute liver injury.
• The findings offer valuable insights for improving the delivery and efficacy of other poorly soluble natural compounds.