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

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.

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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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The authors declare that they have no conflict of interest.

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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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Keywords

  • Porcine islets
  • Exenatide
  • Microspheres
  • Microcapsules
  • Islet encapsulation
  • Islet xenotransplantation