Transdermal drug delivery targeted to xenobiotics ABC transporters expressed in the skin

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670011
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: KATO Yukio 金沢大学, 薬学系, 教授 (30251440)
• Co-Investigator(Renkei-kenkyūsha): NAKAMICHI Noritaka 金沢大学, 薬学系, 准教授 (10401895) ; WAKAYAMA Tomohiko 金沢大学, 医学系, 准教授 (70305100)
• Research Collaborator: KANO Satoshi
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 経皮吸収 / 貼付剤 / 添加剤 / トランスポーター / ドラッグデリバリー

Outline of Final Research Achievements

Breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) are ATP binding cassette (ABC) transporters which are expressed in various organs including skin and pump out various xenobiotics compounds from the cells. The present study was designed to find excipients used in transdermal pharmaceutics which exert potential inhibition of these dermal ABC transporters with an aim to possible control of drug disposition inside the skin. We searched various excipients and found several compounds which inhibit BCRP function. Their inhibition constant for BCRP was correlated with calculated value of octanol/water partition coefficient (xlogP). One of such excipients inhibited BCRP-mediated transcellular transport of its substrate and reduced distribution of rhodamine 123 into dermis and circulating blood after transdermal administration. The present finding thus suggests possible strategy for control of dermal ABC transporter using pharmaceutical excipients.

Free Research Field

薬物動態学