title: Designing anti-diabetic β-cells microcapsules using polystyrenic sulfonate, polyallylamine, and a tertiary bile acid: Morphology, bioenergetics, and cytokine analysis.
abstract: Recently sodium alginate (SA)-poly-l-ornithine (PLO) microcapsules containing pancreatic β-cells that showed good morphology but low cell viability (<27%) was designed. In this study, two new polyelectrolytes, polystyrenic sulfonate (PSS; at 1%) and polyallylamine (PAA; at 2%) were incorporated into a microencapsulated-formulation, with the aim of enhancing the physical properties of the microcapsules. Following incorporation, the structural characteristics and cell viability were investigated. The effects of the anti-inflammatory bile acid, ursodeoxycholic acid (UDCA), on microcapsule morphology, size, and stability as well as β-cell biological functionality was also examined.
  
  
  
  Microcapsules were prepared using PLO-PSS-PAA-SA mixture and two types of microcapsules were produced: without UDCA (control) and with UDCA (test). Microcapsule morphology, stability, and size were examined. Cell count, microencapsulation efficiency, cell bioenergetics, and activity were also examined.
  
  
  
  The new microcapsules showed good morphology but cell viability remained low (29% ± 3%). UDCA addition improved cell viability post-microencapsulation (42 ± 5, P < 0.01), reduced swelling (P < 0.01), improved mechanical strength (P < 0.01), increased Zeta-potential (P < 0.01), and improved stability. UDCA addition also increased insulin production (P < 0.01), bioenergetics (P < 0.01), and decreased β-cell TNF-α (P < 0.01), IFN-gamma (P < 0.01), and IL-6 (P < 0.01) secretions.
  
  
  
  Addition of 4% UDCA to a formulation system consisting of 1.8% SA, 1% PLO, 1% PSS, and 2% PAA enhanced cell viability post-microencapsulation and resulted in a more stable formulation with enhanced encapsulated β-cell metabolism, bioenergetics, and biological activity with reduced inflammation. This suggests potential application of UDCA, when combined with SA, PLO, PSS, and PAA, in β-cell microencapsulation and diabetes treatment. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:501-509, 2016.
authors.affiliation: Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Inst., Curtin University, Perth, Western Australia, 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 Inst., Curtin University, Perth, Western Australia, 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 Inst., Curtin University, Perth, Western Australia, Australia.
authors.forename: Hani
authors.initials: H
authors.lastname: Al-Salami
authors.affiliation: Harry Perkins Inst. of Medical Research, Centre for Diabetes Research, Perth, Western Australia, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
authors.affiliation: Harry Perkins Inst. of Medical Research, Centre for Diabetes Research, Perth, Western Australia, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Jamieson
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis*; D004339:Drug Compounding; D015195:Drug Design; D004734:Energy Metabolism / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011137:Polystyrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001647:Bile Acids and Salts; D016207:Cytokines; D007004:Hypoglycemic Agents; D011073:Polyamines; D011137:Polystyrenes; D013451:Sulfonic Acids; C063994:polyallylamine
keywords: bile acid; biomaterials; microencapsulation; pancreatic β-cells; type 1 diabetes