Topical delivery of keloid therapeutic drug, tranilast, by combined use of oleic acid and propylene glycol as a penetration enhancer: evaluation by skin microdialysis in rats.
Topical delivery of tranilast (N-(3,4-dimethoxycinnamoyl)anthranic acid), an inhibitor of collagen synthesis and a therapeutic drug for keloid and hypertrophic scar, was examined, in rats, with oleic acid alone or a combination of oleic acid and propylene glycol as penetration enhancer. Evaluation was by measurement of the concentration of tranilast in plasma and in the dialysate from skin microdialysis. When tranilast at a dose of 1.5 mg was applied topically as an ethanol solution containing 5% polyvinylpyrrolidone on a dorsal skin surface (2.25 cm2), the maximum concentration of tranilast in skin dialysate was approximately 2 microM. When 10 or 20% oleic acid was added to the same ethanol solution the maximum concentration of tranilast in the dialysate increased to 10-20 microM, and this value was further increased to 60 microM by the addition of a combination of oleic acid (10 or 20%) and propylene glycol (10%) to the solution. With the combination of oleic acid and propylene glycol the area under the plot of the concentration of tranilast in skin dialysate against time between 0 and 4 h (AUC0-4) was more than 400-fold that after intravenous administration. The transdermal bioavailability of tranilast as assessed by the AUC0-4 of tranilast in plasma, was 0.2% of the dose applied in the ethanol solution, 3-5% of that applied in the ethanol solution containing oleic acid, and 14-16% of that applied in the ethanol solution containing both oleic acid and propylene glycol. These results suggest that the topical delivery of tranilast with an absorption enhancer such as a mixture of oleic acid and propylene glycol might be a more effective medication than oral administration of tranilast for the treatment of keloid and hypertrophic scar.
Murakami
T
T
Department of Biopharmaceutics, Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Yoshioka
M
M
Yumoto
R
R
Higashi
Y
Y
Shigeki
S
S
Ikuta
Y
Y
Yata
N
N
D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004337:Drug Carriers; D008297:Male; D017551:Microdialysis; D019301:Oleic Acid; D019946:Propylene Glycol; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000493:pharmacokinetics*
D018926:Anti-Allergic Agents; D004337:Drug Carriers; D062367:ortho-Aminobenzoates; D019301:Oleic Acid; D019946:Propylene Glycol; C012293:tranilast