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Novel complexation hydrogels for oral peptide delivery: In vitro evaluation of their cytocompatibility and insulin‐transport enhancing effects using Caco‐2 cell monolayers
Author(s) -
Ichikawa Hideki,
Peppas Nicholas A.
Publication year - 2003
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.10128
Subject(s) - monolayer , chemistry , self healing hydrogels , caco 2 , ethylene glycol , nuclear chemistry , cytotoxicity , polymerization , insulin , methacrylic acid , in vitro , peptide , polymer , polymer chemistry , biochemistry , organic chemistry , medicine , endocrinology
Poly[methacrylic acid‐grafted‐poly(ethylene glycol)] [P(MAA‐ g ‐EG)] is a complexation hydrogel molecularly designed for oral peptide delivery. In this work, the cytotoxicity and insulin‐transport enhancing effect of P(MAA‐ g ‐EG) microparticles on intestinal epithelial cells were evaluated using Caco‐2 cell monolayers. A series of P(MAA‐ g ‐EG) microparticles with different polymer compositions were prepared by a photo‐initiated free radical solution polymerization and subsequent pulverization. The hydrogel microparticles were preswollen in either Ca 2+ ‐containing (CM+) or Ca 2+ ‐free medium (CM−; pH 7.4) and applied to the apical side of the Caco‐2 monolayers. No significant cytotoxic effects, as determined by a calorimetric assay with P(MAA‐ g ‐EG) microparticles preswollen in the CM+, were observed at doses ranging from 3 to 31 mg/cm 2 of cell monolayer. Transepithelial electrical resistance (TEER) measurements showed that the P(MAA‐ g ‐EG) microparticles induced a Ca 2+ concentration‐dependent lowering in TEER values. The reduction effect in CM− media was greater than that in CM+ media (17 ± 2% reduction in CM+ and 45 ± 3% reduction in CM−, respectively). Insulin transport in the presence of the preswollen P(MAA‐ g ‐EG) microparticles was also strongly depended on the Ca 2+ concentration in the medium. The respective estimated permeability for insulin alone and the insulin with hydrogels in CM+ were 0.77 and 1.16 × 10 −8 cm/s, whereas those in CM− were 1.18 and 24.78 × 10 −8 cm/s. The results demonstrate that the P(MAA‐ g ‐EG) hydrogel microparticles could be used as a cytocompatible carrier possessing the transport‐enhancing effect of insulin on the intestinal epithelial cells. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 609–617, 2003