Quantification of insulin release from implantable polymer-based delivery systems and augmentation of therapeutic effect with simultaneous release of somatostatin.
Insulin injections control diabetes mellitus but do not reproduce physiologic regulation. Polymer-based controlled-release technology has enabled us to demonstrate: that the controlled release of insulin from polymer matrices can indeed be used to control diabetes mellitus but does so at the expense of hyperinsulinemia and hypoglycemia; and that somatostatin can be delivered in similar fashion, so as to provide glucose homeostasis in a more physiologic range, at lower insulin levels and at somatostatin doses below those used in intermittent infusion studies; and, that microgram quantities of a drug can be delivered successfully in vivo with intact biological function and in a manner that can be monitored continuously. In the present study the simultaneous polymer-matrix-controlled release of insulin with somatostatin extended glycemic control in diabetic rats. Eleven rats received subcutaneous polymer matrix implants containing insulin alone and 11 rats received implants containing insulin and somatostatin. Plasma and urinary glucose control were improved in both groups. Glucose concentrations in the insulin alone group remained depressed for 5 days until insulin release from the matrices declined below 11.6 units/kg/day. When somatostatin was delivered at 0.75-1.1 micrograms/kg/day together with insulin, plasma glucose control persisted for 12 days until insulin release decreased below 3.6 units/kg/day. It is our hope that further experiments regarding the potential role of both controlled-release devices and somatostatin will be performed to provide continuing therapeutic alternatives to the insulin-dependent diabetic. This is also the first in vivo demonstration of the simultaneous release of two biologically active peptide hormones from polymer matrices. The use of the polymer matrix systems may not only have profound effects on the ambulatory care of diabetes but might also permit the investigation of the synergistic effects of other families of compounds.
Edelman
E R
ER
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Brown
L
L
Langer
R
R
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005260:Female; D006400:Hematocrit; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000008:administration & dosage*
D007328:Insulin; D013004:Somatostatin