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Probucol (PB) is a highly lipophilic drug with potential protective effects on pancreatic β-cells from inflammation and oxidation. PB has poor bioavailability and solubility, and despite many attempts, significant improvement in antidiabetic effects or absorption has yet to be discovered. Recently, the role of bile acids has been established in significant drug formulation stabilisation effects and as cell-penetrating agents. Promising results in pharmaceutical formulation studies on drug stability and release patterns when lithocholic acid (LCA) is conjugated with PB and sodium alginate (SA) have been demonstrated. Thus, this study aimed to develop and characterise PB microcapsules incorporating LCA and examine the biological effects of the microcapsules in vitro and in vivo. PB/LCA microcapsules were prepared using an encapsulation method, ionic gelation vibrational jet flow technology. LCA incorporation in PB microcapsules showed positive effects on β-cells with improved insulin release, antioxidant activity, and PB intracellular uptake. Diabetic mice gavaged LCA-PB microcapsules showed a significant reduction in diabetes signs and symptoms, better survival rate, reduced blood glucose levels, and pro-inflammatory cytokines, with an increase PB level in blood and tissues suggesting a potential therapy for treating diabetes mellitus. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules' morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel. [ABSTRACT FROM AUTHOR]