Semi-interpenetrating network (Sipn) co-electrospun gelatin/insulin fiber formulation for transbuccal insulin delivery

Leyuan Xu, Natasha Sheybani, Shunlin Ren, Gary L. Bowlin, William Andrew Yeudall, Hu Yang

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)275-285
Number of pages11
JournalPharmaceutical Research
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Interpenetrating polymer networks
Gelatin
Insulin
Fibers
Scaffolds
Eosine Yellowish-(YS)
Bioactivity
Degradation
Permeability
Mechanical properties
Drug Compounding
Phosphorylation
Mouth Mucosa
Electrospinning
Drug delivery
Adipocytes
Polymerization

Keywords

  • electrospun gelatin fiber
  • insulin
  • semi-interpenetrating network
  • transbuccal delivery

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Semi-interpenetrating network (Sipn) co-electrospun gelatin/insulin fiber formulation for transbuccal insulin delivery. / Xu, Leyuan; Sheybani, Natasha; Ren, Shunlin; Bowlin, Gary L.; Yeudall, William Andrew; Yang, Hu.

In: Pharmaceutical Research, Vol. 32, No. 1, 01.01.2015, p. 275-285.

Research output: Contribution to journalArticle

Xu, Leyuan ; Sheybani, Natasha ; Ren, Shunlin ; Bowlin, Gary L. ; Yeudall, William Andrew ; Yang, Hu. / Semi-interpenetrating network (Sipn) co-electrospun gelatin/insulin fiber formulation for transbuccal insulin delivery. In: Pharmaceutical Research. 2015 ; Vol. 32, No. 1. pp. 275-285.
@article{a5bf0c125875486cb386361f8841a95c,
title = "Semi-interpenetrating network (Sipn) co-electrospun gelatin/insulin fiber formulation for transbuccal insulin delivery",
abstract = "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.",
keywords = "electrospun gelatin fiber, insulin, semi-interpenetrating network, transbuccal delivery",
author = "Leyuan Xu and Natasha Sheybani and Shunlin Ren and Bowlin, {Gary L.} and Yeudall, {William Andrew} and Hu Yang",
year = "2015",
month = "1",
day = "1",
doi = "10.1007/s11095-014-1461-9",
language = "English (US)",
volume = "32",
pages = "275--285",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Semi-interpenetrating network (Sipn) co-electrospun gelatin/insulin fiber formulation for transbuccal insulin delivery

AU - Xu, Leyuan

AU - Sheybani, Natasha

AU - Ren, Shunlin

AU - Bowlin, Gary L.

AU - Yeudall, William Andrew

AU - Yang, Hu

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - electrospun gelatin fiber

KW - insulin

KW - semi-interpenetrating network

KW - transbuccal delivery

UR - http://www.scopus.com/inward/record.url?scp=84934759151&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84934759151&partnerID=8YFLogxK

U2 - 10.1007/s11095-014-1461-9

DO - 10.1007/s11095-014-1461-9

M3 - Article

C2 - 25030186

AN - SCOPUS:84934759151

VL - 32

SP - 275

EP - 285

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 1

ER -