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