Morphological, Stability, and Hypoglycemic Effects of New Gliclazide-Bile Acid Microcapsules for Type 1 Diabetes Treatment: the Microencapsulation of Anti-diabetics Using a Microcapsule-Stabilizing Bile Acid

Abstract

© 2018, American Association of Pharmaceutical Scientists. When we administered orally a mixture of the anti-diabetic drug, gliclazide (G) and a primary bile acid, they exerted a hypoglycemic effect in a rat model of type 1 diabetes (T1D), but stability of mixture was limited. We aimed to develop and characterize microcapsules incorporating G with a microcapsule-stabilizing bile acid, ursodeoxycholic acid (UDCA). Sodium alginate (SA)-based microcapsules were prepared with either G or G with UDCA and analyzed in terms of morphological, physico-chemical, and electro-chemical characteristics at different pH and temperatures. The microcapsules’ effects on viability on muscle cell line (C2C12) and on diabetic rats’ blood glucose levels and inflammatory profiles were also examined. Bile acid-based microcapsules maintained their morphology, showed good stability, and compatibility profiles, and the incorporation of UDCA resulted in less G content per microcapsule (p < 0.01) and production of stronger microcapsules that were more resistant to mechanical pressure (p < 0.01). G-UDCA-SA microcapsules enhanced muscle cell viability at higher glucose concentrations compared with control (G-SA and UDCA-SA), and they had strong anti-inflammatory effects on diabetic rats. In addition, the incorporation of UDCA into G microcapsules enhanced the physical characteristics of the microcapsules and optimized G delivery after oral administration.