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AAPS PharmSciTech

, Volume 19, Issue 7, pp 3009–3018 | Cite as

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

  • Sangeetha Mathavan
  • Nigel Chen-Tan
  • Frank Arfuso
  • Hani Al-Salami
Research Article

Abstract

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.

KEY WORDS

drug stability ursodeoxycholic acid diabetes microencapsulation cell viability 

Notes

Acknowledgments

The authors acknowledge the Curtin Health Innovation Research Institute for provision of laboratory space and technology platforms utilized in this study. The authors would also like to acknowledge Professor Deidre Coombe from the School of Biomedical Sciences at Curtin University for the generous donation of the C2C12 cell line. HAS is partially supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 690876.

Funding Information

The authors acknowledge the Curtin CUPS Scholarship for their support and also acknowledge the use of equipment, scientific, and technical assistance of the Curtin University Electron Microscope Facility, which has been partially funded by the University, State and Commonwealth Governments.

Compliance with Ethical Standards

Disclosure

The authors declare that they have no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Sangeetha Mathavan
    • 1
  • Nigel Chen-Tan
    • 2
  • Frank Arfuso
    • 3
  • Hani Al-Salami
    • 4
  1. 1.Biotechnology and Drug Development Research Laboratory, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research InstituteCurtin UniversityPerthAustralia
  2. 2.Faculty of Science and EngineeringCurtin UniversityPerthAustralia
  3. 3.Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research InstituteCurtin UniversityPerthAustralia
  4. 4.School of PharmacyCurtin UniversityPerthAustralia

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