Pharmacological and Biological Study of Microencapsulated Probucol-Secondary Bile Acid in a Diseased Mouse Model

Abstract

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.

Taurine Grafted Micro-Implants Improved Functions without Direct Dependency between Interleukin-6 and the Bile Acid Lithocholic Acid in Plasma

“…Mice weight and blood glucose were monitored as described above and based on the ethics approved by the Animal Ethics Committee at Curtin University. For diabetes confirmation, glucose and insulin levels were assessed as per our well-established methods [ 26 , 63 , 64 ]. For assessment of the inflammatory profile, concentrations of the proinflammatory cytokines interleukin-6 (IL-6), interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), interleukin-12 (IL-12), and concentrations of the anti-inflammatory cytokine interleukin-ten (IL-10) were all measured.…”

The Effect of Deoxycholic Acid on Chitosan-Enabled Matrices for Tissue Scaffolding and Injectable Nanogels

“…C2C12 were grown in DMEM (10% FBS and 1% penicillin-streptomycin) following protocol for non-differentiated myotubes [ 55 ]. NIT-1 were grown in DMEM (supplemented with 10% FBS, 5.5 mmol glucose), Sigma-Aldrich, MO, USA), and free amino acids following a published protocol [ 56 ]. The cells were incubated in a humidified atmosphere of 5% CO 2 at 37 °C.…”

“…A Visco-88 viscometer (Malvern Instruments, Malvern, UK) was utilised for viscosity, torque, shear stress, and shear rate measurements [ 56 ]. The Zeta potential was determent using a 3000HS Zetasizer (Malvern, UK).…”

Pharmacological Dose-Effect Profiles of Various Concentrations of Humanised Primary Bile Acid in Encapsulated Cells

“…Measurements of antioxidant activity were taken using a plate reader (Enspire, PerkinElmer, Waltham, MA, USA) for fluorescence, with increased fluorescent readings indicating increased oxidative stress, and therefore, decreased antioxidant activity. Oxidative stress measurements were taken from oxidized radical species following incubation with a mixture of dichloro-dihydro-fluorescein diacetate and 2,2 -azobis-2-methyl-propanimidamide dihydrochloride [25,37,38]. Assessments were taken under glycaemic and hyperglycaemic conditions.…”