Primary Bile Acid Chenodeoxycholic Acid-Based Microcapsules to Examine ß-cell Survival and the Inflammatory Response
MetadataShow full item record
In past studies using hydrogel-polyelectrolyte matrix and different bile acid excipients, we microencapsulated pancreatic ß-cells using various methods, and the microcapsules were mechanically stable, displayed good morphological characteristics with good physico-chemical compatibility but had limited cell viability and poor cell survival. Using bile acids, cell survival increased but overall remained limited. Thus, this study aimed to test different microencapsulating methods and examine the effects of the primary hydrophobic bile acid, chenodeoxycholic acid (CDCA), on ß-cell microcapsules, in terms of morphology and cell function. Using the polymer sodium alginate (SA) and the co-polymer poly-l-ornithine (PLO), in 10:1 ratio, two microcapsules were made, one without CDCA and one with CDCA. During the microencapsulation process, polymer flow rate and culture media flow rate were screened (0.1–1.5 mL/min) for most uniform microcapsule. Pancreatic ß-cells (NIT-1) were microencapsulated and tested for morphology, formulation physico-chemical compatibility, stability, surface topography and chemical composition. Encapsulated cell viability, metabolism, respiration, bioenergetics, biological activity and the inflammatory profile were also measured. A polymer flow rate of 0.8 mL/min accompanied by 0.6 mL/min media flow rate were found to produce the most uniform microcapsules using 10:1 formulation ratio. The microcapsules showed poor cell viability which was improved significantly after CDCA incorporation. CDCA also enhanced insulin secretion (p < 0.01), metabolism, respiration and bioenergetics (p < 0.01) and significantly reduced the inflammatory response. These benefits were attained without compromising microcapsule size or stability. A polymer flow rate of 0.8 mL/min and a media flow rate of 0.6 mL/min produced good microcapsules when using SA and PLO in 10:1 ratio, and the incorporation of the primary bile acid, chenodeoxycholic acid, enhanced microcapsule stability and significantly increased cell survival and reduced inflammation which suggests potential applications in ß-cell microencapsulation and transplantation.
Showing items related by title, author, creator and subject.
A new biotechnological microencapsulating methodology utilising individualized gradient-screened jet laminar flow techniques for pancreatic ß-cell delivery: bile acids support cell energy-generating mechanisms.Mooranian, A.; Negrulj, R.; Takechi, R.; Jamieson, E.; Morahan, G.; Al-Salami, Hani (2017)IIntroduction: In previous studies, we developed a new technique (Ionic Gelation Vibrational Jet Flow; IGVJF) in order to encapsulate pancreatic ß-cells, for insulin in vivo delivery, and diabetes treatment. The fabricated ...
Alginate-deoxycholic Acid Interaction and Its Impact on Pancreatic ?-Cells and Insulin Secretion and Potential Treatment of Type 1 DiabetesMooranian, Armin; Negrulj, Rebecca; Al-Salami, Hani (2016)© 2016. Springer Science+Business Media New York.Introduction: The secondary bile acid, deoxycholic acid (DCA), has been shown to exert membrane stabilising effects on a pH sensitive delivery system for the oral delivery ...
The Influence of Stabilized Deconjugated Ursodeoxycholic Acid on Polymer-Hydrogel System of Transplantable NIT-1 CellsMooranian, A.; Negrulj, R.; Al-Salami, Hani (2016)Purpose: The encapsulation of pancreatic ß-cells in biocompatible matrix has generated great interest in diabetes treatment. Our work has shown improved microcapsules when incorporating the bile acid ursodeoxycholic acid ...