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The incorporation of water-soluble gel matrix into bile acid-based microcapsules for the delivery of viable β-cells of the pancreas, in diabetes treatment: biocompatibility and functionality studies

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Abstract

In recent studies, we microencapsulated pancreatic β-cells using sodium alginate (SA) and poly-L-ornithine (PLO) and the bile acid, ursodeoxycholic acid (UDCA), and tested the morphology and cell viability post-microencapsulation. Cell viability was low probably due to limited strength of the microcapsules. This study aimed to assess a β-cell delivery system which consists of UDCA-based microcapsules incorporated with water-soluble gel matrix. The polyelectrolytes, water-soluble gel (WSG), polystyrenic sulphate (PSS), PLO and polyallylamine (PAA) at ratios 4:1:1:2.5 with or without 4 % UDCA, were incorporated into our microcapsules, and cell viability, metabolic profile, cell functionality, insulin production, levels of inflammation, microcapsule morphology, cellular distribution, UDCA partitioning, biocompatibility, thermal and chemical stabilities and the microencapsulation efficiency were examined. The incorporation of UDCA with PSS, PAA and WSG enhanced cell viability per microcapsule (p < 0.05), cellular metabolic profile (p < 0.01) and insulin production (p < 0.01); reduced the inflammatory release TNF-α (p < 0.01), INF-gamma (p < 0.01) and interleukin-6 (IL-6) (p < 0.01); and ceased the production of IL-1β. UDCA, PSS, PAA and WSG addition did not change the microencapsulation efficiency and resulted in biocompatible microcapsules. Our designed microcapsules showed good morphology and desirable insulin production, cell functionality and reduced inflammatory profile suggesting potential applications in diabetes.

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References

  1. Chang TM, Johnson LJ, Ransome OJ. Semipermeable aqueous microcapsules. IV. nonthrombogenic microcapsules with heparin-complexed membranes. Can J Physiol Pharmacol. 1967;45(4):705–15.

    Article  PubMed  CAS  Google Scholar 

  2. Negrulj R, Mooranian A, Al-Salami H. Potentials and limitations of bile acids in type 2 diabetes mellitus: applications of microencapsulation as a novel oral delivery system. J Endocrinol Diabetes Mellitus. 2013;1(2):49–59.

    Google Scholar 

  3. Lim GJ, Zare S, Van DM, Atala A. Cell microencapsulation. Adv Exp Med Biol. 2010;670:126–36.

    Article  PubMed  CAS  Google Scholar 

  4. Chang TM. Therapeutic applications of polymeric artificial cells. Nat Rev Drug Discov. 2005;4(3):221–35.

    Article  PubMed  CAS  Google Scholar 

  5. Calafiore R, Basta G. Clinical application of microencapsulated islets: actual prospectives on progress and challenges. Adv Drug Deliv Rev. 2013.

  6. Mooranian A, Negrulj R, Chen-Tan N, Fakhoury M, Arfuso F, Jones F, et al. Advanced bile acid-based multi-compartmental microencapsulated pancreatic beta-cells integrating a polyelectrolyte-bile acid formulation, for diabetes treatment. Artif Cells Nanomed Biotechnol. 2014:1–8

  7. Mooranian A, Negrulj R, Arfuso F, Al-Salami H. Characterization of a novel bile acid-based delivery platform for microencapsulated pancreatic β-cells. Artif Cells Nanomed Biotechnol. 2014(0):1–7

  8. Souza YE, Chaib E, Lacerda PG, Crescenzi A, Bernal-Filho A, D’Albuquerque LA. Islet transplantation in rodents. Do encapsulated islets really work? Arq Gastroenterol. 2011;48(2):146–52.

    Article  PubMed  Google Scholar 

  9. de Vos P, Lazarjani HA, Poncelet D, Faas MM. Polymers in cell encapsulation from an enveloped cell perspective. Adv Drug Deliv Rev. 2013.

  10. Dominguez-Bendala JPA and Ricordi C. islet cell therapy and pancreatic stem cells. 2013;2:835–53.

  11. Mineo D, Sageshima J, Burke GW, Ricordi C. Minimization and withdrawal of steroids in pancreas and islet transplantation. Transpl Int. 2009;22(1):20–37.

    Article  PubMed  Google Scholar 

  12. Weir GC. Islet encapsulation: advances and obstacles. Diabetologia. 2013;56(7):1458–61.

    Article  PubMed  CAS  Google Scholar 

  13. Beck J, Angus R, Madsen B, Britt D, Vernon B, Nguyen KT. Islet encapsulation: strategies to enhance islet cell functions. Tissue Eng. 2007;13(3):589–99.

    Article  PubMed  CAS  Google Scholar 

  14. Hamaguchi K, Gaskins HR, Leiter EH. NIT-1, a pancreatic beta-cell line established from a transgenic NOD/Lt mouse. Diabetes. 1991;40(7):842–9.

    Article  PubMed  CAS  Google Scholar 

  15. Mooranian A, Negrulj R, Arfuso F, Al-Salami H. Characterization of a novel bile acid-based delivery platform for microencapsulated pancreatic beta-cells. Artif Cells Nanomed Biotechnol. 2014:1–7.

  16. Mooranian A, Negrulj R, Chen-Tan N, Al-Sallami HS, Fang Z, Mukkur T, et al. Novel artificial cell microencapsulation of a complex gliclazide-deoxycholic bile acid formulation: a characterization study. Drug Des Devel Ther. 2014;8:1003.

    PubMed  PubMed Central  Google Scholar 

  17. Mooranian A, Negrulj R, Mathavan S, Martinez J, Sciarretta J, Chen-Tan N, et al. An advanced microencapsulated system: a platform for optimized oral delivery of antidiabetic drug-bile acid formulations. Pharm Dev Technol. 2015;20(6):702–9.

    PubMed  CAS  Google Scholar 

  18. Mooranian A, Negrulj R, Chen-Tan N, Watts GF, Arfuso F, Al-Salami H. An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid) as a permeation enhancer. Drug Des Devel Ther. 2014;8:1673–83.

    PubMed  CAS  PubMed Central  Google Scholar 

  19. Mooranian A, Negrulj R, Chen-Tan N, Al-Sallami HS, Fang Z, Mukkur T, et al. Microencapsulation as a novel delivery method for the potential antidiabetic drug. Probucol Drug Des Devel Ther. 2014;8:1221–30.

    PubMed  CAS  Google Scholar 

  20. Uludag H, Sefton MV. Colorimetric assay for cellular activity in microcapsules. Biomaterials. 1990;11(9):708–12.

    Article  PubMed  CAS  Google Scholar 

  21. Mooranian A, Negrulj R, Mikov M, Golocorbin-Kon S, Arfuso F, Al-Salami H. Novel chenodeoxycholic acid-sodium alginate matrix in the microencapsulation of the potential antidiabetic drug, probucol. An in vitro study. J Microencapsul. 2015;32(6):589–97.

    PubMed  CAS  Google Scholar 

  22. Donath MY, Böni-Schnetzler M, Ellingsgaard H, Ehses JA. Islet inflammation impairs the pancreatic β-cell in type 2 diabetes. Physiology (Bethesda, Md). 2009;24:325–31.

    Article  CAS  Google Scholar 

  23. Perez MJ, Briz O. Bile-acid-induced cell injury and protection. World J Gastroenterol. 2009;15(14):1677–89.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Stepanov V, Stankov K, Mikov M. The bile acid membrane receptor TGR5: a novel pharmacological target in metabolic, inflammatory and neoplastic disorders. J Recept Signal Transduct Res. 2013;33(4):213–23.

    Article  PubMed  CAS  Google Scholar 

  25. Brand Martin D, Nicholls DG. Assessing mitochondrial dysfunction in cells. Biochem J. 2011;435(Pt 2):297–312.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Wu M, Neilson A, Swift AL, Moran R, Tamagnine J, Parslow D, et al. Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells. Am J Physiol Cell Physiol. 2007;292(1):C125–36.

    Article  PubMed  CAS  Google Scholar 

  27. Arai T, Wilson DL, Kasai N, Freddi G, Hayasaka S, Tsukada M. Preparation of silk fibroin and polyallylamine composites. J Appl Polym Sci. 2002;84(11):1963–70.

    Article  CAS  Google Scholar 

  28. Gill P, Moghadam TT, Ranjbar B. Differential scanning calorimetry techniques: applications in biology and nanoscience. J Biomol Tech. 2010;21(4):167.

    PubMed  PubMed Central  Google Scholar 

  29. Lamcharfi L, Meyer C, Lutton C. Rationalization of the relative hydrophobicity of some common bile acids by infrared and Raman spectroscopy. Biospectroscopy. 1997;3(5):393–401.

    Article  CAS  Google Scholar 

  30. Darrabie MD, Kendall Jr WF, Opara EC. Characteristics of poly-L-ornithine-coated alginate microcapsules. Biomaterials. 2005;26(34):6846–52.

    Article  PubMed  CAS  Google Scholar 

  31. Tam SK, Dusseault J, Polizu S, Ménard M, Hallé J-P, Yahia LH. Physicochemical model of alginate–poly-L-lysine microcapsules defined at the micrometric/nanometric scale using ATR-FTIR, XPS, and ToF-SIMS. Biomaterials. 2005;26(34):6950–61.

    Article  PubMed  CAS  Google Scholar 

  32. Tam S, Bilodeau S, Dusseault J, Langlois G, Hallé J-P, Yahia L. Biocompatibility and physicochemical characteristics of alginate–polycation microcapsules. Acta Biomater. 2011;7(4):1683–92.

    Article  PubMed  CAS  Google Scholar 

  33. Bhatia SR, Khattak SF, Roberts SC. Polyelectrolytes for cell encapsulation. Curr Opin Colloid Interface Sci. 2005;10(1):45–51.

    Article  CAS  Google Scholar 

  34. de Vos P, Faas MM, Strand B, Calafiore R. Alginate-based microcapsules for immunoisolation of pancreatic islets. Biomaterials. 2006;27(32):5603–17.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors acknowledge Australian Postgraduate Award (APA) and Curtin Research Scholarship (CRS) and acknowledge the use of laboratory equipment, scientific and technical assistance of the Curtin University, Electron Microscope Facility, which has been partially funded by the University, State and Commonwealth Governments. The authors acknowledge the Pharmaceutical Technology Laboratory (Curtin School of Pharmacy) and acknowledge the ARC Centre of Excellence in Plant Energy Biology (UWA) for the access to equipment. The authors acknowledge the generous donation of NIT-1 cells from Professor Grant Morahan at the University of Western Australia.

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  1. Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA, Australia

    Armin Mooranian, Rebecca Negrulj & Hani Al-Salami

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  1. Armin Mooranian
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  2. Rebecca Negrulj
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  3. Hani Al-Salami
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Correspondence to Hani Al-Salami.

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Mooranian, A., Negrulj, R. & Al-Salami, H. The incorporation of water-soluble gel matrix into bile acid-based microcapsules for the delivery of viable β-cells of the pancreas, in diabetes treatment: biocompatibility and functionality studies. Drug Deliv. and Transl. Res. 6, 17–23 (2016). https://doi.org/10.1007/s13346-015-0268-5

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