Characterization of glucose-mediated insulin release from implantable polymers.

Abstract:

:We characterized a glucose-sensitive, controlled-release insulin delivery system. Insulin release rates increased when glucose was perfused in the release media surrounding the matrix. The system was composed of solid, particulate insulin, incorporated into an ethylene-vinyl acetate copolymer (EVAc) matrix. Feedback control was mediated by the glucose oxidase enzyme immobilized to Sepharose beads, which were incorporated along with insulin into the EVAc matrix. When glucose in solution entered the insulin delivery system, gluconic acid was produced, causing a drop in the microenvironmental pH of the matrix. This fall in pH resulted in a rise in insulin solubility and consequently a rise in the insulin release rate from the matrix. Insulin concentrations increased in vitro and in vivo in response to glucose infusion. The increased insulin release was shown to consist of a finite pulse of insulin that required an optimal recovery period of 1 h to achieve a maximal repeated response to a glucose stimulus. Repeated pulses were demonstrated over a 4 h period. An optimum enzyme ratio was also determined.

journal_name

J Pharm Sci

authors

Brown LR,Edelman ER,Fischel-Ghodsian F,Langer R

doi

10.1021/js9600686

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

1341-5

issue

12

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)50203-7

journal_volume

85

pub_type

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