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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]

Bile acids have recently been studied for potential applications as formulation excipients and enhancers for drug release; however, some bile acids are not suitable for this application. Unconjugated lithocholic acid (ULCA) has recently shown drug formulation-stabilizing and anti-inflammatory effects. Lipophilic drugs have poor gut absorption after an oral dose, which necessitates the administration of high doses and causes subsequent side effects. Probucol (PB) is a highly lipophilic drug with poor oral absorption that resulted in restrictions on its clinical prescribing. Hence, this study aimed to design new delivery systems for PB using ULCA-based matrices and to test drug formulation, release, temperature, and biological effects. ULCA-based matrices were formulated for PB oral delivery by applying the jet-flow microencapsulation technique using sodium alginate as a polymer. ULCA addition to new PB matrices improved the microcapsule's stability, drug release in vitro (formulation study), and showed a promising effect in ex vivo study (p < 0.05), suggesting that ULCA can optimize the oral delivery of PB and support its potential application in diabetes treatment. [ABSTRACT FROM AUTHOR]