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

Phytosterols are a class of natural steroids found in various plants. Commercially available phytosterols (PS) are primarily extracted from the deodorized distillate of soybean oil and consist predominantly of β-sitosterol with smaller amounts of stigmasterol and campesterol. Numerous studies have consistently demonstrated the significant lipid-lowering activity of PS. However, the application of PS is limited due to their low oral bioavailability. To enhance the water solubility and in turn the absorption of PS at the molecular level, microcapsule-like cocrystals were designed using bile acids via hydrogen bonding. As expected, four microcapsule-like cocrystals were successfully prepared: β-sitosterol with cholic acid (CA) and chenodeoxycholic acid (CDCA), and PS with CA and CDCA. The cocrystal of PS with CA (PS-CA) was selected for further investigation, and the results demonstrated that PS-CA exhibited significantly enhanced solubility <i>in vitro</i> and markedly improved oral bioavailability <i>in vivo</i>. Specifically, the AUC_{1-24 h} of PS-CA was 6 times that of PS, while the <i>C</i>_max was 4 times. Moreover, as a result of the improved bioavailability of PS, PS-CA showed superior lipid-lowering activity.