A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

Abstract

Context: Gliclazide (G) is a commonly prescribed drug for Type 2 diabetes (T2D). In a recent study, we found that when G was combined with a primary bile acid, and gavaged to an animal model of Type 1 diabetes (T1D), it exerted a hypoglycemic effect. We hypothesized this to be due to metabolic activation of the primary bile acid into a secondary or a tertiary bile acid, which enhanced G solubility and absorption. The tertiary bile acid, taurocholic acid (TCA), has shown strong permeation-enhancing effects in vivo. Thus, we aimed to design, characterize, and test microcapsules incorporating G and TCA in an animal model of T1D.

Methods: Microcapsules were prepared using the polymer sodium alginate (SA). G-SA microcapsules (control) and G–TCA–SA microcapsules (test) were extensively examined (in-vitro) at different pH and temperatures. The microcapsules were gavaged to diabetic rats, and blood glucose and G concentrations in serum were examined. Ex-vivo studies were also performed using a muscle cell line (C2C12), and cell viability and glucose intake post-treatment were examined.

Results: G–TCA–SA microcapsules showed good stability, uniformity, and thermal and chemical excipient compatibilities. TCA did not change the size or the shape of the microcapsules, but it enhanced their mechanical resistance and reduced their swelling properties. G–TCA–SA enhanced the viability of C2C12 cells over 24 hours, and exerted a hypoglycemic effect in alloxan-induced type-1 diabetic rats.

Conclusions: The incorporation of TCA into G-microcapsules resulted in functionally improved microcapsules with a positive effect on cell viability and glycemic control in Type-1 diabetic animals.

Keywords:

• Microencapsulation
• permeation
• structure
• taurocholic acid
• Type 1 diabetes

Acknowledgements

The authors would like to extend sincere thanks to Professor Deirdre Coombe for providing the muscle cell lines (C2C12). The authors also acknowledge the Pharmaceutical Technology Laboratory (Curtin School of Pharmacy).

Declaration of interest

The authors declare that there is no conflict of interest. The authors acknowledge Curtin Research Scholarship (CRS) granted from Curtin University for their support. The authors also acknowledge the CHIRI at Curtin University, and the Curtin-seeding grant for support to Hani Al-Salami. Sangeetha Mathavan was a recipient of a Curtin University CUPS Scholarship. We also acknowledge the use of laboratory equipment, scientific and technical assistance of the Curtin University, Electron Microscope Facility, which has been partially funded by the University, State and Commonwealth Governments.