Common therapy for diabetes mellitus is subcutaneous administration of insulin that is subject to serious disadvantages, such as patient noncompliance and occasional hypoglycemia. Hence, oral administration of insulin could be more convenient and serve as a desired route. However, oral administration of insulin is severely limited by the low bioavailability of insulin through the gastrointestinal tract. In this study, a semi-interpenetrating network gelatin fiber scaffold (sIPN GF) was fabricated for oral mucosal delivery of insulin as an alternative route. This sIPN GF was engineered from an electrospun gelatin fiber scaffold (GF), which was further crosslinked with polyethylene glycol diacrylate (PEG-DA) to enhance its stability. Within the crosslinking process, eosin Y served as a photoinitiator, and the ratio of PEG-DA to eosin Y was optimized with respect to cytocompatibility and degradation rate. The results showed that the fabricated scaffold morphology, mechanical properties, and degradation rate were significantly enhanced after the crosslinking process. This optimized formulation was used to fabricate sIPN gelatin-co-insulin fiber scaffold (sIPN GIF). Enzyme-linked immunosorbent assay (ELISA) was used to monitor the insulin releasing kinetics of sIPN GIF. Western blot analysis showed that sIPN GIF activated intracellular AKT phosphorylation in a releasing time-dependant manner. Oil red O staining confirmed the released insulin was able to induce 3T3-L1 preadipocyte differentiation. The permeability of insulin from sIPN GIF was determined on the order of 10^-7 cm/s using a vertical Franz diffusion cell system mounted with porcine buccal mucosa. These findings suggest that sIPN GIF holds a great potential for oral mucosal delivery of insulin.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-4190 |
| Date | 29 July 2013 |
| Creators | Xu, Leyuan |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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