PH-SENSITIVE LIPOSOMES COMPOSED OF PHOSPHATIDYLETHANOLAMINE AND FATTY-ACID

pH-induced destabilization, aggregation and fusion of liposomes composed of phosphatidylethanolamine (PE) and various fatty acid were studied. Destabilization was examined as a fluorescent change caused by leakage of coencapsulated aminonaphthalene-3,6,8-trisulfonic acid (ANTS) and N,N-p-xylylenebispyridinium bromide (DPX). Fusion was monitored by two different methods, that is, intermixing assay of internal aqueous contents of liposomes, and lipid dilution assay of liposomes labeled with fluorescent phospholipids. Contents leakage from liposomes was observed by lowering the pH, and pH where the leakage began depended on fatty acid used. Fifty percent leakage of contents from PE liposomes containing α-hydroxypalmitic acid or α-hydroxystearic acid was observed at pH 5.5, that from liposomes containing stearic acid or palmitic acid was observed at pH 6.5—6.7, and that from ricinoleic acid at pH 7.2. Aggregation and fusion of the respective liposomes also occurred at a similar pH region. These results were interpreted by the notion that the protonation of the fatty acid triggers a series of pH-sensitive events. The liposomes developed in this study may be useful as a drug carrier which could release the contents in response to pH changes in their environment. © 1990, The Pharmaceutical Society of Japan. All rights reserved.