Abstract
The antilipidemic drug, probucol (PB), has demonstrated potential applications in Type 2 diabetes (T2D) through its protective effects on pancreatic β-cells. PB has poor solubility and bioavailability, and despite attempts to improve its oral delivery, none has shown dramatic improvements in absorption or antidiabetic effects. Preliminary data has shown potential benefits from bile acid co-encapsulation with PB. One bile acid has shown best potential improvement of PB oral delivery (ursodeoxycholic acid, UDCA). This study aimed to examine PB and UDCA microcapsules (with UDCA microcapsules serving as control) in terms of the microcapsules’ morphology, biological effects ex vivo, and their hypoglycemic and antilipidemic and anti-inflammatory effects in vivo. PBUDCA and UDCA microcapsules were examined in vitro (formulation studies), ex vivo and in vivo. PBUDCA microcapsules exerted positive effects on β-cells viability at hyperglycemic state, and brought about hypoglycemic and anti-inflammatory effects on the prediabetic mice. In conclusion, PBUDCA co-encapsulation have showed beneficial therapeutic impact of dual antioxidant-bile acid effects in diabetes treatment.
Highlights
The antilipidemic drug, probucol (PB), has demonstrated potential applications in Type 2 diabetes (T2D) through its protective effects on pancreatic β-cells
Of the endogenous bile acids, the tertiary bile acid ursodeoxycholic acid (UDCA) has been shown to be the most potent anti-inflammatory and anti-apoptotic bile acid with significant cell protective properties with its mechanism of action being correlated with its cellular uptake by muscle and β-cells[15,16,17,18,19,20]
In PBUDCA microcapsules compared with UDCA microcapsules, there was a new peak in the 3470–3155 cm−1 region as well as alternations in peak-bond activity in the 1715–1345 cm−1 region
Summary
The antilipidemic drug, probucol (PB), has demonstrated potential applications in Type 2 diabetes (T2D) through its protective effects on pancreatic β-cells. Other studies involving human clinical trials have shown that UDCA is well tolerated and exerts positive effects on glucose and energy homeostasis[22,23,24] Many bile acids such as chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) have shown to be affected by the development and progression of insulin-resistance and diabetes, as well as associated-inflammation[4,5,25,26]. To date and to the best of our knowledge, no studies have examined PBUDCA pharmaceutical properties, their effects on both pancreatic β-cells and muscle cells, their cellular uptake, permeation and interaction with the ABC protein transporters Multi-Resistance Associated Proteins (MRP) 1, 2 and 3, and the preclinical long-term efficacy of these microcapsules on glucose regulation, lipid and inflammatory profiles, as well as their effects on the bile acid profile, in a mouse model of insulin-resistance. The study is a continuation of ongoing work in our laboratory examining the preclinical efficacy of dual ingredient antioxidant-bile acid microcapsules in diabetes mellitus with published hypoglycaemic effects of controlled groups[3,11,14,27,28,29,30,31,32,33,34,35]
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