Antihyperglycemic Effect of Insulin from Self-Dissolving Micropiles in Dogs

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As a percutaneous delivery device, self-dissolving micropiles (SDMPs) composed of chondroitin sulfate and insulin were prepared under room temperature from highly concentrated solution, glue. The mean weight of SDMP was 1.03±0.04mg. One insulin SDMP was percutaneously administered to the shaved abdominal skin of four beagle dogs at insulin dose level of 1.0 and 2.0IU/dog. After administration, blood samples were collected for 6h and plasma glucose levels were measured. The time when minimum plasma glucose level appeared, T_<min>, was 1.38±0.2h for 1.0IU study and 1.38±0.1h for 2.0IU study and clear dose-dependent hypoglycemic effect of insulin was observed in the dose range. By comparing the area above the plasma glucose level vs. time curve (AAC) between insulin SDMP and subcutaneous (s.c.) injection solution, the relative pharmacological availabilities were 99% (1.0IU) and 90% (2.0IU), respectively. To ascertain the usefulness of insulin SDMP, oral glucose tolerance test (OGTT) was performed. When dogs were treated with insulin SDMPs, 2.0IU, followed by an OGTT 30min, glycemia did not appear for 5h. On the other hand, when OGTT was performed at 1h after insulin SDMP administration, hypoglycemia appeared as in the case of s.c. injection of insulin solution, 2.0IU. Insulin SDMP improved the oral glucose challenge for 3h, with a maximum effect at 30min before the administration of glucose. Those results suggest the usefulness of a SDMP for the percutaneous delivery of peptide/protein drugs like insulin.
公益社団法人日本薬学会の論文
2008-03-01

Antihyperglycemic Effect of Insulin from Self-Dissolving Micropiles in Dogs

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