Preparation and characterization of a glucose-responsive insulin-releasing polymer device.
A new glucose-responsive insulin delivery system composed of phenylboronic acid (PBA) groups was prepared and investigated. Complexation of various diol-containing molecules with PBA gel beads was evaluated using frontal chromatography. The structural features of the diol-containing molecules strongly influenced their binding to PBA gel beads. In particular, open-chain monosaccharides demonstrated higher association constants (ca 9.5 x 10(2) to 5.1 x 10(3) l/mol) than glucose (ca 6.3 x 10(2) l/mol). Furthermore, a model system utilizing a fluorescent derivative of tris(hydroxymethyl)aminomethane was synthesized and bound to PBA gel beads. The molecules were released in a pulsatile manner in response to glucose. In addition, gluconic acids were chemically attached to insulin molecules. The modified insulin, containing two gluconic acid units per insulin molecule, was isolated using ion-exchange chromatography. This gluconic acid-modified insulin (G-Ins) was bound onto a PBA gel column, and the G-Ins release profile in response to varying glucose concentrations was investigated. The results demonstrate that the PBA gel beads release G-Ins in response to glucose concentration. Thus, this new system may be applied for self-regulated insulin delivery.
International Center for Biomaterials Science, Chiba, Japan.
D
D
Shiino
Y
Y
Murata
K
K
Kataoka
Y
Y
Koyama
M
M
Yokoyama
T
T
Okano
Y
Y
Sakurai
D000818:Animals; D001665:Binding Sites; D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D050260:Carbohydrate Metabolism; D002852:Chromatography, Ion Exchange; D016503:Drug Delivery Systems; D005452:Fluoresceins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006900:Hydroxylation; D007328:Insulin / Q000008:administration & dosage*; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D011108:Polymers; D011409:Propylene Glycols / Q000378:metabolism
D001897:Boronic Acids; D005452:Fluoresceins; D007328:Insulin; D008689:Methacrylates; D011108:Polymers; D011409:Propylene Glycols; C087934:5-tris(hydroxymethyl)methylamino-2-(3,6-dihydroxy-9H-xanthen-10-yl)benzoate; C087935:3-methacrylamidophenylboronic acid; D005947:Glucose