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Elucidation of the Mechanism of Enhanced Insulin Uptake and Release from pH Responsive Hydrogels
Author(s) -
Tuesca Anthony,
Lowman Anthony
Publication year - 2008
Publication title -
macromolecular symposia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.257
H-Index - 76
eISSN - 1521-3900
pISSN - 1022-1360
DOI - 10.1002/masy.200850619
Subject(s) - insulin , self healing hydrogels , chemistry , ethylene glycol , monomer , polymerization , insulin glargine , polyelectrolyte , polymer , polymer chemistry , medicine , organic chemistry , hypoglycemia
Summary: Environmentally responsive hydrogels composed of poly(methacrylic acid‐g‐ethylene glycol) (P(MAA‐g‐EG)) have shown promise for oral insulin delivery due to their pH responsive complexation behavior. A series of hydrogel formulations were polymerized with varying amounts of crosslinker and varying monomer volume fraction. The mesh size of the network depended primarily on pH, varying from 8.0 to 27.2 nm. Insulin loading efficiency varied directly with crosslink density, ranging from 42.7 to 84.9% of available insulin loaded into the hydrogels. The release of insulin was performed with each polymer formulation at 5 pH levels ranging from 2.7 to 6.8. Insulin release was less than 20% for all formulations tested with insulin for the duration of the 3 hour release study for all pH levels considered except when the pH was 6.8, at which point the release occurred as a burst. Loading studies performed with insulin glargine, an insulin analog with an increased pI, showed the same trends as native insulin. However, the release of insulin glargine only occurred at a pH level above that of the pI of the protein. These results indicate that hydrogen bonds and ionic interactions between the protein and P(MAA‐g‐EG) may strongly influence its loading and release behavior in vitro .