Bile Acid-based Microcapsule-Like Cocrystals of Phytosterols with Enhanced Solubility, Bioavailability, and...

Area of Science:

• Pharmacology
• Materials Science
• Biochemistry

Background:

• Phytosterols (PS) are plant-derived steroids with demonstrated lipid-lowering properties.
• The therapeutic application of PS is hindered by poor oral bioavailability and low water solubility.
• Novel formulation strategies are needed to enhance PS absorption and efficacy.

Purpose of the Study:

• To develop microcapsule-like cocrystals of phytosterols (PS) with bile acids to improve water solubility and oral bioavailability.
• To investigate the in vitro and in vivo performance of these novel PS cocrystals.
• To evaluate the impact of enhanced bioavailability on the lipid-lowering activity of PS.

Main Methods:

• Cocrystal formation using hydrogen bonding between phytosterols (PS) and bile acids (cholic acid and chenodeoxycholic acid).
• Preparation and characterization of four types of microcapsule-like cocrystals.
• In vitro solubility assessments and in vivo pharmacokinetic studies (AUC and Cmax) of the optimized PS-bile acid cocrystal (PS-CA).
• Comparison of lipid-lowering activity between PS-CA and native PS.

Main Results:

• Four microcapsule-like cocrystals were successfully synthesized, including PS with cholic acid (PS-CA).
• The PS-CA cocrystal demonstrated significantly enhanced solubility in vitro.
• In vivo studies revealed a 6-fold increase in AUC(1-24h) and a 4-fold increase in Cmax for PS-CA compared to PS.
• PS-CA exhibited superior lipid-lowering activity due to improved oral bioavailability.

Conclusions:

• Microcapsule-like cocrystal formation with bile acids is an effective strategy to enhance phytosterol (PS) water solubility and oral bioavailability.
• The PS-CA cocrystal represents a promising formulation for improving the therapeutic efficacy of phytosterols.
• This approach holds potential for developing more effective lipid-lowering agents based on phytosterols.