Similarities of Transport Characteristics of Lipophilic Cations between Porcine Kidney Epithelial LLC-PK₁ Cells and 5-Component Liposomes

Abstract

In the previous study, we prepared phosphatidylcholine (PC) liposomes and phosphatidylserine (PS)-containing PC/PS liposomes, and investigated the uptake characteristics of lipophilic organic cations. The uptake of bisoprolol into PC/PS liposomes was significantly greater than that into PC liposomes. In the present study, we prepared the 5-component liposomes containing PC, PS, phosphatidylethanolamine, sphingomyelin, and cholesterol, and compared the uptake characteristics of lipophilic organic cations into the liposomes with that into porcine kidney LLC-PK 1 cells. The uptake of flecainide was significantly inhibited by lipophilic diphenhydramine (DPH) both in 5-component liposomes and in LLC-PK 1 cells, but not by hydrophilic tetraethylammonium. The 50 ％ inhibitory concentration (IC 50 value) for the DPH-sensitive uptake of flecainide was 1.08 mM and 657 µ M in the 5-component liposomes and LLC-PK 1 cells, respectively. In addition, the uptake of the various 11 cationic compounds both into the 5-component liposomes and into LLC-PK 1 cells was significantly correlated with their lipophilicity (Log D) values and their polar surface area (Log PSA) values. Collectively, the uptake characteristics of lipophilic cations in the 5-component liposomes was considerably similar to that of the postulated H + /lipophilic cation antiport system in LLC-PK 1 cells.