Glucagon-like Peptide-1 Functionalized PEG Hydrogels Promote Survival and Function of Encapsulated Pancreatic Beta-cells

Overview

Journal Biomacromolecules

Publisher American Chemical Society

Specialties Biochemistry
Biology
Molecular Biology

Date 2009 Jul 10

PMID 19586041

Citations 39

Authors

Chien-Chi Lin

Kristi S Anseth

Affiliations

Soon will be listed here.

Abstract

Encapsulating pancreatic islets in a semipermeable poly(ethylene glycol) (PEG) hydrogel membrane holds potential as an immuno-isolation barrier for the treatment of type 1 diabetes mellitus. The semipermeable PEG hydrogel not only permits free diffusion of nutrients, metabolic waste, and insulin produced from the encapsulated beta-cells, but also provides a size-exclusion effect to prevent direct contact of entrapped islets to host immune cells and antibodies. However, the use of unmodified PEG hydrogels for islet encapsulation is not ideal, as there is no bioactive cue to promote the long-term survival and function of the encapsulated cells. Herein, we report the synthesis and characterization of a bioactive glucagon-like peptide 1 (GLP-1) analog, namely, GLP-1-cysteine or GLP-1C, and the fabrication of functional GLP-1 immobilized PEG hydrogels via a facile thiol-acrylate photopolymerization. The immobilization of bioactive GLP-1C within PEG hydrogels is efficient and does not alter the bulk hydrogel properties. Further, the GLP-1 immobilized PEG hydrogels enhance the survival and insulin secretion of encapsulated islets. Overall, this study demonstrates a strategy to modify PEG hydrogels with bioactive peptide moieties that can significantly enhance the efficacy of islet encapsulation.

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References

Bonner-Weir S, Weir G . New sources of pancreatic beta-cells. Nat Biotechnol. 2005; 23(7):857-61. DOI: 10.1038/nbt1115. View

Youn Y, Chae S, Lee S, Kwon M, Shin H, Lee K . Improved peroral delivery of glucagon-like peptide-1 by site-specific biotin modification: design, preparation, and biological evaluation. Eur J Pharm Biopharm. 2007; 68(3):667-75. DOI: 10.1016/j.ejpb.2007.07.009. View

Chae S, Jin C, Shin H, Youn Y, Lee S, Lee K . Preparation, characterization, and application of biotinylated and biotin-PEGylated glucagon-like peptide-1 analogues for enhanced oral delivery. Bioconjug Chem. 2007; 19(1):334-41. DOI: 10.1021/bc700292v. View

Cheung C, Anseth K . Synthesis of immunoisolation barriers that provide localized immunosuppression for encapsulated pancreatic islets. Bioconjug Chem. 2006; 17(4):1036-42. DOI: 10.1021/bc060023o. View

Peppas N, Wood K, Blanchette J . Hydrogels for oral delivery of therapeutic proteins. Expert Opin Biol Ther. 2004; 4(6):881-7. DOI: 10.1517/14712598.4.6.881. View

Brubaker P, Drucker D . Minireview: Glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology. 2004; 145(6):2653-9. DOI: 10.1210/en.2004-0015. View

Youn Y, Jeon J, Chae S, Lee S, Lee K . PEGylation improves the hypoglycaemic efficacy of intranasally administered glucagon-like peptide-1 in type 2 diabetic db/db mice. Diabetes Obes Metab. 2007; 10(4):343-6. DOI: 10.1111/j.1463-1326.2007.00823.x. View

Lee S, Lee S, Youn Y, Na D, Chae S, Byun Y . Synthesis, characterization, and pharmacokinetic studies of PEGylated glucagon-like peptide-1. Bioconjug Chem. 2005; 16(2):377-82. DOI: 10.1021/bc049735+. View

Lee S, Youn Y, Lee S, Byun Y, Lee K . PEGylated glucagon-like peptide-1 displays preserved effects on insulin release in isolated pancreatic islets and improved biological activity in db/db mice. Diabetologia. 2006; 49(7):1608-11. DOI: 10.1007/s00125-006-0234-3. View

10.

Lewis E, Shapiro L, Bowers O, Dinarello C . Alpha1-antitrypsin monotherapy prolongs islet allograft survival in mice. Proc Natl Acad Sci U S A. 2005; 102(34):12153-8. PMC: 1189344. DOI: 10.1073/pnas.0505579102. View

11.

Kim S, Bae Y . Long-term insulinotropic activity of glucagon-like peptide-1/polymer conjugate on islet microcapsules. Tissue Eng. 2005; 10(11-12):1607-16. DOI: 10.1089/ten.2004.10.1607. View

12.

Lin C, Metters A . Enhanced protein delivery from photopolymerized hydrogels using a pseudospecific metal chelating ligand. Pharm Res. 2006; 23(3):614-22. DOI: 10.1007/s11095-005-9395-x. View

13.

Weber L, Anseth K . Hydrogel encapsulation environments functionalized with extracellular matrix interactions increase islet insulin secretion. Matrix Biol. 2008; 27(8):667-73. PMC: 2631362. DOI: 10.1016/j.matbio.2008.08.001. View

14.

Wilson J, Chaikof E . Challenges and emerging technologies in the immunoisolation of cells and tissues. Adv Drug Deliv Rev. 2007; 60(2):124-45. PMC: 2736629. DOI: 10.1016/j.addr.2007.08.034. View

15.

Drucker D . Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology. 2002; 122(2):531-44. DOI: 10.1053/gast.2002.31068. View

16.

Cruise G, Hegre O, Scharp D, Hubbell J . A sensitivity study of the key parameters in the interfacial photopolymerization of poly(ethylene glycol) diacrylate upon porcine islets. Biotechnol Bioeng. 1999; 57(6):655-65. DOI: 10.1002/(sici)1097-0290(19980320)57:6<655::aid-bit3>3.0.co;2-k. View

17.

Wu J, Chen X, Cao X, Baker M, Kaufman D . Cytokine-induced metabolic dysfunction of MIN6 beta cells is nitric oxide independent. J Surg Res. 2001; 101(2):190-5. DOI: 10.1006/jsre.2001.6285. View

18.

Owens D, Zinman B, Bolli G . Alternative routes of insulin delivery. Diabet Med. 2003; 20(11):886-98. DOI: 10.1046/j.1464-5491.2003.01076.x. View

19.

Steil G, Panteleon A, Rebrin K . Closed-loop insulin delivery-the path to physiological glucose control. Adv Drug Deliv Rev. 2004; 56(2):125-44. DOI: 10.1016/j.addr.2003.08.011. View

20.

Weber L, Hayda K, Haskins K, Anseth K . The effects of cell-matrix interactions on encapsulated beta-cell function within hydrogels functionalized with matrix-derived adhesive peptides. Biomaterials. 2007; 28(19):3004-11. DOI: 10.1016/j.biomaterials.2007.03.005. View