Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis.
Iontophoresis is a promising technique for enhancing transdermal administration of charged drugs. However, conventional iontophoresis is not sufficient for effective delivery of large, hydrophilic, or electrically neutral molecules. In this study, we utilized charged liposomes as carriers, focused on a transfollicular route for delivery of the liposomes, and optimized iontophoretic conditions and lipid composition for this method in both in vitro and in vivo conditions. As a result, we identified the optimum condition (lipid composition: DOTAP/EPC/Chol=2:2:1, current supply: 0.45mA/cm(2), duration: 1h) for effective iontophoretic delivery of aqueous solution, which cannot be transferred into the skin without charged liposomes. We also examined the pharmacological effects of iontophoresis of liposomes encapsulating insulin (INS-lipo) using a rat model of type I diabetes. Interestingly, iontophoresis of INS-lipo onto a diabetes rat skin resulted in a gradual decrease in blood glucose levels, with levels reaching 20% of initial values at 18h after administration. These lower blood glucose levels were maintained for up to 24h. Significant amount of insulin were also detected in plasma 18h after iontophoresis of INS-lipo. We succeeded in developing a non-invasive and persistent transfollicular drug delivery system that used a combination of liposomes and iontophoresis.
Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
Kazuaki
K
Kajimoto
Masahiko
M
Yamamoto
Misuzu
M
Watanabe
Kaoru
K
Kigasawa
Kiyoshi
K
Kanamura
Hideyoshi
H
Harashima
Kentaro
K
Kogure
D000279:Administration, Cutaneous; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism; D018859:Hair Follicle / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D007478:Iontophoresis; D008081:Liposomes; D008297:Male; D018613:Microscopy, Confocal; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply / Q000378:metabolism; D012869:Skin Absorption
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008081:Liposomes; D004364:Pharmaceutical Preparations