Pharmacological and Biological Study of Microencapsulated Probucol-Secondary Bile Acid in a Diseased Mouse Model
Susbin Raj Wagle,
Bozica Kovacevic,
Corina Mihaela Ionescu,
Daniel Walker,
Melissa Jones,
Louise Carey,
Ryusuke Takechi,
Momir Mikov,
Armin Mooranian,
Hani Al-Salami
Affiliations
Susbin Raj Wagle
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Bozica Kovacevic
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Corina Mihaela Ionescu
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Daniel Walker
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Melissa Jones
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Louise Carey
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Ryusuke Takechi
School of Population Health, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Momir Mikov
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21101 Novi Sad, Serbia
Armin Mooranian
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Hani Al-Salami
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
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.
