Semi-interpenetrating network (sIPN) co-electrospun gelatin/insulin fiber formulation for transbuccal insulin delivery. Pharm Res 2015 Jan;32(1):275-85
Date
07/18/2014Pubmed ID
25030186DOI
10.1007/s11095-014-1461-9Scopus ID
2-s2.0-84934759151 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
PURPOSE: This work was aimed at developing a semi-interpenetrating network (sIPN) co-electrospun gelatin/insulin fiber scaffold (GIF) formulation for transbuccal insulin delivery.
METHODS: Gelatin was electrospun into fibers and converted into an sIPN following eosin Y-initiated polymerization of polyethylene glycol diacrylate (PEG-DA). The cytocompatibility, degradation rate and mechanical properties were examined in the resulting sIPNs with various ratios of PEG-DA to eosin Y to find a suitable formulation for transbuccal drug delivery. Insulin was co-electrospun with gelatin into fibers and converted into an sIPN-GIF using this suitable formulation. The in vitro release kinetics of insulin was evaluated using ELISA. The bioactivity of released insulin was analyzed in 3T3-L1 preadipocytes using Western blotting and Oil Red O staining. The transbuccal permeability of released insulin was determined using an in vitro porcine oral mucosa model.
RESULTS: The sIPN-GF formulation of GF cross-linked by PEG-DA (1% w/v) with eosin Y (5% v/v) possessed no cytotoxic effect, a moderate degradation rate with degradation half-life of 49 min, and a significant enhancement in mechanical properties. This formulation was used to fabricate sIPN-GIF. Insulin release was extended up to 4 h by sIPN-GIF. The released insulin successfully triggered intracellular AKT phosphorylation and induced adipocyte differentiation in 3T3-L1 preadipocytes. The transbuccal permeability of released insulin was determined on the order of 10(-7) cm/s.
CONCLUSIONS: Insulin can be fabricated into an sIPN-GIF formulation following co-electrospinning and cross-linking without losing bioactivity. It proved the potential of this new formulation for transbuccal insulin delivery.
Author List
Xu L, Sheybani N, Ren S, Bowlin GL, Yeudall WA, Yang HAuthor
Hu Yang PhD Chair, Professor in the Biomedical Engineering department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
3T3-L1 CellsAdministration, Buccal
Animals
Cell Culture Techniques
Cross-Linking Reagents
Drug Carriers
Drug Liberation
Gelatin
Hypoglycemic Agents
Insulin
Mice
Microscopy, Electron, Scanning
Mouth Mucosa
Permeability
Polyethylene Glycols
Surface Properties
Swine
Technology, Pharmaceutical