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Original Article

Insulin micropiles comprising biodegradable polymers for production of a long-term hypoglycemic effect

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Pages 212-218 | Received 17 Nov 2009, Accepted 22 Apr 2010, Published online: 14 Jun 2010
 

Abstract

As a percutaneous sustained-release preparation, insulin micropiles (MPs) were prepared with biodegradable polymers poly(lactic acid) (PLA), poly(ϵ-caprolactone) (PCL) and poly(lactic-co-glycolic acid) (PLGA) as the base. The obtained PLA, PCL, and PLGA MPs of which the insulin:polymer ratio was 1:2 were administered to rat skin at 40 IU/kg and hypoglycemic effects measured for 6 days. The order of the hypoglycemic effect was PLA>PCL>PLGA. PLA MP showed the strongest hypoglycemic effect (2 days). The hypoglycemic effect of insulin PLA MP was dependent on the formulation; the order was insulin:PLA (2:1)>insulin:PLA (1:1)>insulin:PLA (1:2). As the ratio of insulin to the polymer base increased, the hypoglycemic effect increased. The area above the plasma glucose levels vs. time curves for 6 days from insulin:PLA (2:1) MPs, 10, 20, 30, and 40 IU/ kg, were 249 ± 108, 2003 ± 379, 3960 ± 794, and 6311 ± 726%·h. A dose-dependent hypoglycemic effect was obtained at 10–40 IU/kg and pharmacological availabilities were 11.1%, 44.5%, 58.6%, and 70%, respectively. Insulin:PLA (2:1) MP showed high plasma insulin level, 86.9–134.7 IU/mL, for 3 days. There was no damage to rat skin. These results suggest the usefulness of insulin:PLA (2:1) MP as a sustained-release percutaneous delivery system for insulin.

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