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Sustained exenatide delivery via intracapsular microspheres for improved survival and function of microencapsulated porcine islets

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Abstract

The ability of glucagon-like peptide-1 analogs to enhance glucose-dependent insulin secretion and to inhibit β cell apoptosis could be of potential benefit for islet transplantation. In this study, we investigated the effect of sustained local delivery of exenatide, a synthetic exendin-4, on the in vitro viability and function of encapsulated porcine islets. Prior to encapsulation, we fabricated exenatide-loaded poly(latic-co-glycolic acid) microspheres, and investigated their release behavior with different initial drug-loading amounts. Exenatide-loaded microspheres, exhibiting a sustained release over 21 days, were subsequently chosen and co-encapsulated with porcine islets in alginate microcapsules. During the 21-day period, the islets co-encapsulated with the exenatide-loaded microspheres exhibited improved survival and glucose-stimulated insulin secretion, compared to those without. This suggested that the intracapsular sustained delivery of exenatide via microspheres could be a promising strategy for improving survival and function of microencapsulated porcine islets for islet xenotransplantation.

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Acknowledgements

This work was carried out in part in the Frederick Seitz Materials Research Laboratory Central Facilities and Beckman Institute for Advanced Science and Technology, University of Illinois.

Funding

Financial support for this work was partially provided by the Research Board and Kim-Fund of the University of Illinois.

Author information

Author notes

  1. In-Yong Kim

    Present address: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea

Authors and Affiliations

  1. Department of Electrical and Computer Engineering, University of Illinois, Urbana, IL, 61801, USA

    Benjamin Lew, In-Yong Kim, Hyungsoo Choi & Kyekyoon (Kevin) Kim

  2. Micro and Nanotechnology Laboratory, University of Illinois, Urbana, IL, 61801, USA

    Hyungsoo Choi & Kyekyoon (Kevin) Kim

  3. Department of Bioengineering, University of Illinois, Urbana, IL, 61801, USA

    Kyekyoon (Kevin) Kim

  4. Department of Materials Science and Engineering, University of Illinois, Urbana, IL, 61801, USA

    Kyekyoon (Kevin) Kim

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  1. Benjamin Lew
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Correspondence to Hyungsoo Choi or Kyekyoon (Kevin) Kim.

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All institutional and national guidelines for the care and use of laboratory animals were followed.

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Lew, B., Kim, IY., Choi, H. et al. Sustained exenatide delivery via intracapsular microspheres for improved survival and function of microencapsulated porcine islets. Drug Deliv. and Transl. Res. 8, 857–862 (2018). https://doi.org/10.1007/s13346-018-0484-x

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  • DOI: https://doi.org/10.1007/s13346-018-0484-x

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