Percutaneous absorption of interferon-α by self-dissolving micropiles

Abstract

To ascertain the pharmaceutical usefulness of self-dissolving micropiles (SDMPs) containing interferon (IFN), two types of SDMPs were prepared using chondroitin sulfate and dextran as the base. After percutaneous administration of 5000 IU/kg IFN-α2b SDMP to rats, serum IFN levels were measured for 6 h. The peak serum IFN level, maximum drug concentration (Cmax), and the time when serum IFN level reaches to Cmax, time to reach maximum concentration (Tmax), were 8.2 ± 0.5 IU/ml and 1.2 ± 0.1 h, respectively, for chondroitin SDMP. For dextran SDMP, Cmax and Tmax were 3.1 ± 0.4 IU/ml and 3.3 ± 0.3 h, respectively. AUC of chondroitin SDMP was 1.5 times greater than that of dextran SDMP. Bioavailabilities (BAs) of IFN were 378.3% for chondroitin SDMP and 255.9% for dextran SDMP that were larger than 100%. The BA of IFN from subcutaneous (s.c.) injection solution was 320.9%. The relative BAs of IFN SDMPs against s.c. injection solution were 117.8% for chondroitin SDMP and 79.9% dextran SDMP. An in vitro release experiment suggested the faster release rate of IFN from chondroitin SDMP, 57.3% at 5 min, than dextran SDMP, 32.6% at 5 min. Chondroitin SDMP containing IFN showed good stability for 3 months and no damage to the administered rat skin.