title: Semi-interpenetrating network (sIPN) co-electrospun gelatin/insulin fiber formulation for transbuccal insulin delivery.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843067, Richmond, Virginia, 23284, USA, lxu3@vcu.edu.
authors.forename: Leyuan
authors.initials: L
authors.lastname: Xu
authors.forename: Natasha
authors.initials: N
authors.lastname: Sheybani
authors.forename: Shunlin
authors.initials: S
authors.lastname: Ren
authors.forename: Gary L
authors.initials: GL
authors.lastname: Bowlin
authors.forename: W Andrew
authors.initials: WA
authors.lastname: Yeudall
authors.forename: Hu
authors.initials: H
authors.lastname: Yang
mesh_terms: D041721:3T3-L1 Cells; D000278:Administration, Buccal; D000818:Animals; D018929:Cell Culture Techniques; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005780:Gelatin / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009061:Mouth Mucosa / Q000378:metabolism; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties; D013552:Swine; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols; D005780:Gelatin