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

    Access Status
    Open access via publisher
    Authors
    Mathavan, Sangeetha
    Chen-Tan, N.
    Arfuso, Frank
    Al-Salami, Hani
    Date
    2015
    Type
    Journal Article
    
    Metadata
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    Citation
    Mathavan, S. and Chen-Tan, N. and Arfuso, F. and Al-Salami, H. 2015. A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes. Drug Delivery. [In Press].
    Source Title
    Drug Delivery
    DOI
    10.3109/10717544.2015.1110846
    ISSN
    1071-7544
    School
    School of Pharmacy
    URI
    http://hdl.handle.net/20.500.11937/8874
    Collection
    • Curtin Research Publications
    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.

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      Mathavan, S.; Chen-Tan, N.; Arfuso, Frank; Al-Salami, Hani (2018)
      © 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 ...
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      CONTEXT: We have shown that the primary bile acid, cholic acid (CA), has anti-diabetic effects in vivo. Probucol (PB) is a lipophilic drug with potential applications in type 2 diabetes (T2D). OBJECTIVE: This study aimed ...
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