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The effect of a tertiary bile acid, taurocholic acid, on the morphology and physical characteristics of microencapsulated probucol: potential applications in diabetes: a characterization study

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Abstract

In recent studies, we designed multi-compartmental microcapsules as a platform for the targeted oral delivery of lipophilic drugs in an animal model of type 2 diabetes (T2D). Probucol (PB) is a highly lipophilic, antihyperlipidemic drug with potential antidiabetic effects. PB has low bioavailability and high inter-individual variations in absorption, which limits its clinical applications. In a new study, the bile acid, taurocholic acid (TCA), exerted permeation enhancing effects in vivo. Accordingly, this study aimed to design and characterize TCA-based PB microcapsules and examine the effects of TCA on the microcapsules’ morphology, stability, and release profiles. Microcapsules were prepared using the polymer sodium alginate (SA). Two types of microcapsules were produced, one without TCA (PB-SA, control) and one with TCA (PB-TCA-SA, test). Microcapsules were studied in terms of morphology, surface structure and composition, size, drug contents, cross-sectional imaging (using microtomography (Micro-CT) analysis), Zeta potential, thermal and chemical profiles, rheological parameters, swelling, mechanical strength, and release studies at various temperature and pH values. The production yield and the encapsulation efficiency were also studied together with in vitro efficacy testing of cell viability at various glucose concentrations and insulin and TNF-α production using clonal-mouse pancreatic β-cells. PB-TCA-SA microcapsules showed uniform structure and even distribution of TCA within the microcapsules. Drug contents, Zeta potential, size, rheological parameters, production yield, and the microencapsulation efficiency remained similar after TCA addition. In vitro testing showed PB-TCA-SA microcapsules improved β-cell survival under hyperglycemic states and reduced the pro-inflammatory cytokine TNF-α while increasing insulin secretions compared with PB-SA microcapsules. PB-TCA-SA microcapsules also showed good stability, better mechanical (p < 0.01) and swelling (p < 0.01) characteristics, and optimized controlled release at pH 7.8 (p < 0.01) compared with control, suggesting desirable targeted release properties and potential applications in the oral delivery of PB in T2D.

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Acknowledgments

The authors acknowledge the Australian Postgraduate Award (APA) + Curtin Research Scholarship (CRS) for their support. The authors also acknowledge the CHIRI and the use of laboratory equipment and the scientific and technical assistance of Curtin University Electron Microscope Facility, which has been partially funded by the University, State, and Commonwealth Governments. The authors also acknowledge the Pharmaceutical Technology Laboratory (Curtin School of Pharmacy). The authors are grateful to the Harry Perkins Institute of Medical Research, Centre for Medical Research, University of Western Australia and St. Vincent’s Institute of Medical Research (Victoria) for supplying the NIT-1 β-cells.

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, GPO Box U1987, Perth, Western Australia, 6845, Australia

    Armin Mooranian, Rebecca Negrulj & Hani Al-Salami

  2. Stem Cell and Cancer Biology Laboratory, School of Biomedical Science, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia

    Frank Arfuso

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  1. Armin Mooranian
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Mooranian, A., Negrulj, R., Arfuso, F. et al. The effect of a tertiary bile acid, taurocholic acid, on the morphology and physical characteristics of microencapsulated probucol: potential applications in diabetes: a characterization study. Drug Deliv. and Transl. Res. 5, 511–522 (2015). https://doi.org/10.1007/s13346-015-0248-9

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