EFFECT OF PHOSPHATIDYLCHOLINE AND CHOLESTEROL ON PH-SENSITIVE LIPOSOMES

We previously reported that liposomes composed of phosphatidylethanola mine (PE) and fatty acid exhibited pH-dependent leakage, aggregation a nd fusion (N. Hazemoto, M. Harada, N. Komatubara, M. Haga and Y. Kato, Chem. Pharm. Bull., 38, 748 (1990)). In this study, we have examined the effects of phosphatidylcholine (PC) and cholesterol (Chol) on the pH-sensitivity of liposomes. Contents-leakage from liposomes was alway s accompanied by a change in light-scattering, suggesting that aggrega tion or fusion of liposomes causes the leakage. The pH-sensitivity was observed only when liposomes contained less than 32 mol% of PC. The l eakage vs. pH curves shifted to the more acidic regions as the PC cont ent of the liposomes increased, but the maximum leakage (%) did not ch ange. The effect of cholesterol on the pH-sensitivity depended on the PC/PE ratio of the liposomes. Addition of cholesterol to PC/PE/oleic a cid (OA) liposomes system induced two effects, that is, aggregation of liposomes via the reduction in PC content and the stabilization of th e liposomal membrane. It was shown that pH-sensitivity can be controll ed by addition of the appropriate amount of PC and/or Chol to liposoma l lipids.