Percutaneous absorption of interferon-alpha by self-dissolving micropiles.
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-alpha2b 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.
Ito
Yukako
Y
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto, Japan. yukako@mb.kyoto-phu.ac.jp
Saeki
Atsushi
A
Shiroyama
Keiji
K
Sugioka
Nobuyuki
N
Takada
Kanji
K
D000818:Animals; D002809:Chondroitin Sulfates / Q000008:administration & dosage; D003911:Dextrans / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011108:Polymers / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption
D003911:Dextrans; D016898:Interferon-alpha; D011108:Polymers; D002809:Chondroitin Sulfates