Primary Bile Acid Chenodeoxycholic Acid-Based Microcapsules to Examine ß-cell Survival and the Inflammatory Response

Abstract

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.