Sustained-release self-dissolving micropiles for percutaneous absorption of insulin in mice.

Microparticles-adsorbed insulin and zinc insulin (PenfilN) were molded to self-dissolving micropiles (SDMPs) with chondroitin sulfate as the base for the percutaneous administration of insulin. Porous silicon dioxide (Sylysia 320, 440 and 730) and porous calcium silicate (FloriteRE) were used as microparticles. As a reference, insulin loaded SDMPs were prepared. SDMPs were percutaneously administered to mice at the insulin dose level of 2.5 IU/kg. After the insertion of SDMPs to mouse skin, blood samples were collected for 8 h and plasma glucose levels were measured. There were not significant differences on minimum plasma glucose levels between the test preparations. However, T(mins), the time when the minimum glucose level appeared were 1.5 +/- 0.2 h (Sylysia 320), 1.3 +/- 0.2 h (Sylysia 440), 1.6 +/- 0.4 h (Sylysia 730), 2.1 +/- 0.3 h (Florite) and 1.7 +/- 0.3 h (zinc insulin) which were greater than insulin SDMP, 0.8 +/- 0.1 h. In addition, greater hypoglycemic effects were observed with SDMPs containing adsorbent-insulin and/or zinc insulin than insulin SDMP. The mean AACs (area above the plasma glucose level vs. time curve) of SDMPs containing adsorbent-insulin and zinc insulin were 357.8% h for FloriteRE, 333.1% h for Sylysia 320, 308.1% h for Sylysia 440, 328.1% h for Sylysia 730, and 374.7% h for zinc insulin, respectively, which were about two folds higher than that of insulin SDMN, 161.2% h. Those results suggest the usefulness of SDMPs composed of adsorbent-insulin as a long-acting percutaneous insulin preparation.