title: The Influence of Stabilized Deconjugated Ursodeoxycholic Acid on Polymer-Hydrogel System of Transplantable NIT-1 Cells.
abstract: OBJECTIVE
  The encapsulation of pancreatic β-cells in biocompatible matrix has generated great interest in diabetes treatment. Our work has shown improved microcapsules when incorporating the bile acid ursodeoxycholic acid (UDCA), in terms of morphology and cell viability although cell survival remained low. Thus, the study aimed at incorporating the polyelectrolytes polyallylamine (PAA) and poly-l-ornithine (PLO), with the polymer sodium alginate (SA) and the hydrogel ultrasonic gel (USG) with UDCA and examined cell viability and functionality post microencapsulation.
  
  
  METHODS
  Microcapsules without (control) and with UDCA (test) were produced using 1% PLO, 2.5% PAA, 1.8% SA and 4.5% USG. Pancreatic β-cells were microencapsulated and the microcapsules' morphology, surface components, cellular and bile acid distribution, osmotic and mechanical stability as well as biocompatibilities, insulin production, bioenergetics and the inflammatory response were tested.
  
  
  RESULTS
  Incorporation of UDCA at 4% into a PLO-PAA-SA formulation system increased cell survival (p < 0.01), insulin production (p < 0.01), reduced the inflammatory profile (TNF-α, IFN-ϒ, IL-6 and IL-1β; p < 0.01) and improved the microcapsule physical and mechanical strength (p < 0.01).
  
  
  CONCLUSIONS
  β-cell microencapsulation using 1% PLO, 2.5% PAA, 1.8% SA, 4.5% USG and the bile acid UDCA (4%) has good potential in cell transplantation and diabetes treatment.
authors.affiliation: Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
authors.forename: Armin
authors.initials: A
authors.lastname: Mooranian
authors.affiliation: Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Negrulj
authors.affiliation: Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia. hani.al-salami@curtin.edu.au.
authors.forename: Hani
authors.initials: H
authors.lastname: Al-Salami
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D018914:Cells, Immobilized / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D004339:Drug Compounding; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D009997:Osmotic Pressure; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000737:chemistry*
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D007328:Insulin; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D014580:Ursodeoxycholic Acid; D020723:Glucuronic Acid
keywords: artificial cell microencapsulation; bioenergetics; biomaterials; pancreatic β-cells; ursodeoxycholic acid
references.citation: Lancet. 2005 Apr 9-15;365(9467):1333-46
references.pmid: 15823385
references.citation: Diabetes Metab Res Rev. 2011 Jan;27(1):3-13
references.pmid: 21218503
references.citation: Artif Cells Nanomed Biotechnol. 2016 Aug;44(5):1290-7
references.pmid: 25811999
references.citation: Tissue Eng. 2007 Mar;13(3):589-99
references.pmid: 17518605
references.citation: J Lipid Res. 2009 Sep;50(9):1721-34
references.pmid: 19417220
references.citation: Diabetes. 2005 Dec;54 Suppl 2:S108-13
references.pmid: 16306327
references.citation: Cell Death Dis. 2012 Jun 14;3:e322
references.pmid: 22695615
references.citation: Hepatology. 1986 May-Jun;6(3):444-9
references.pmid: 3710433
references.citation: Drug Deliv Transl Res. 2015 Oct;5(5):511-22
references.pmid: 26242686
references.citation: Rev Diabet Stud. 2011 Spring;8(1):51-67
references.pmid: 21720673
references.citation: Biochem Biophys Res Commun. 2010 Jul 9;397(4):735-9
references.pmid: 20541525
references.citation: Trends Biotechnol. 2004 Feb;22(2):87-92
references.pmid: 14757043
references.citation: Pharm Dev Technol. 2015;20(6):702-9
references.pmid: 24798888
references.citation: Biomaterials. 1990 Nov;11(9):708-12
references.pmid: 2090308
references.citation: Biotechnol Prog. 2016 Mar;32(2):501-9
references.pmid: 26748789
references.citation: J Biomed Mater Res A. 2007 Mar 15;80(4):813-9
references.pmid: 17058213
references.citation: Science. 1980 Nov 21;210(4472):908-10
references.pmid: 6776628
references.citation: J Biomed Mater Res A. 2010 Mar 15;92(4):1357-65
references.pmid: 19353563
references.citation: Physiology (Bethesda). 2009 Dec;24:325-31
references.pmid: 19996363
references.citation: J Microencapsul. 2015;32(2):151-6
references.pmid: 25265061
references.citation: Artif Cells Nanomed Biotechnol. 2016;44(1):194-200
references.pmid: 25014218
references.citation: J Biomed Mater Res A. 2008 Dec 15;87(4):1113-22
references.pmid: 18837425
references.citation: Adv Drug Deliv Rev. 2014 Apr;67-68:15-34
references.pmid: 24270009
references.citation: Pharm Dev Technol. 2012 Jan-Feb;17(1):23-9
references.pmid: 20653409
references.citation: J Microencapsul. 2011;28(6):499-507
references.pmid: 21827357
references.citation: World J Gastroenterol. 2009 Apr 14;15(14):1677-89
references.pmid: 19360911
references.citation: Transplant Proc. 2003 Aug;35(5):1625-7
references.pmid: 12962735
references.citation: J Microencapsul. 2005 May;22(3):303-15
references.pmid: 16019916
references.citation: Int Immunopharmacol. 2013 Feb;15(2):372-80
references.pmid: 23246254
references.citation: Drug Deliv Transl Res. 2016 Feb;6(1):17-23
references.pmid: 26671765
references.citation: Curr Diabetes Rev. 2017;13(1):91-96
references.pmid: 26710877
references.citation: J Microencapsul. 1991 Jan-Mar;8(1):83-5
references.pmid: 1880694
references.citation: Transplantation. 2005 Dec 27;80(12):1718-28
references.pmid: 16378067
references.citation: Artif Cells Nanomed Biotechnol. 2016;44(2):588-95
references.pmid: 25358121
references.citation: Adv Drug Deliv Rev. 2014 Apr;67-68:74-83
references.pmid: 24103903
references.citation: Diabetes. 1991 Jul;40(7):842-9
references.pmid: 1647994
references.citation: Eur J Gastroenterol Hepatol. 1997 Dec;9(12):1205-11
references.pmid: 9471027
references.citation: J Microencapsul. 2015;32(6):589-97
references.pmid: 26190214
references.citation: Transplantation. 2010 Nov 27;90(10):1054-62
references.pmid: 20975626
references.citation: In Vivo. 2009 Nov-Dec;23(6):929-35
references.pmid: 20023235
references.citation: J Pharm Innov. 2014;9:150-157
references.pmid: 24829616
references.citation: Drug Des Devel Ther. 2014 Jul 28;8:1003-12
references.pmid: 25114507
references.citation: J Cell Physiol. 1997 Dec;173(3):335-42
references.pmid: 9369946