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

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 activ...

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Main Authors: Mathavan, Sangeetha, Chen-Tan, N., Arfuso, Frank, Al-Salami, Hani
Format: Journal Article
Published: 2015
Online Access:http://hdl.handle.net/20.500.11937/8874
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author Mathavan, Sangeetha
Chen-Tan, N.
Arfuso, Frank
Al-Salami, Hani
author_facet Mathavan, Sangeetha
Chen-Tan, N.
Arfuso, Frank
Al-Salami, Hani
author_sort Mathavan, Sangeetha
building Curtin Institutional Repository
collection Online Access
description 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.
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spelling curtin-20.500.11937-88742017-09-13T14:33:46Z A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes Mathavan, Sangeetha Chen-Tan, N. Arfuso, Frank Al-Salami, Hani 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/8874 10.3109/10717544.2015.1110846 unknown
spellingShingle Mathavan, Sangeetha
Chen-Tan, N.
Arfuso, Frank
Al-Salami, Hani
A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes
title A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes
title_full A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes
title_fullStr A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes
title_full_unstemmed A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes
title_short A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes
title_sort comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of type-1 diabetes
url http://hdl.handle.net/20.500.11937/8874