2010 Fiscal Year Final Research Report

Mechanism of drug-induced phospholipidosis in macrophages

Research Project

Project/Area Number	21790051
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Physical pharmacy
Research Institution	Mukogawa Women's University
Principal Investigator	KURODA Yukihiro Mukogawa Women's University, 薬学部, 准教授 (60314225)
Project Period (FY)	2009 – 2010
Keywords	ホスホリピドーシス / マクロファージ / リポソーム / 塩基性薬物 / 両親媒性薬物
Research Abstract	The mechanism of drug-induced phospholipidosis is unclear. Among hypotheses proposed, two were examined in the present study: i) excessive cellular uptake of phospholipids and ii) neutralization of acidic vesicles by drug accumulation. Phospholipid content in the cells increased by treatment of phospholipidosis-inducing drugs as measured by DiI phospholipid probe. Increased cellular phospholipid accumulation did not decrease following treatment with inhibitors of taking-up pathways. Regardless of their phospholipidosis-inducing potential, drugs characterized by a high pKa value effectively accumulated in liposomes. This accumulation caused an upward shift of the interior pH of liposomes, which was independent of phospholipidosis-inducing potential of drugs.