The pH of malignant tumor cell is about 6.5 as compared to the value of 7.4 for the nornal cells. The pH-sensitive vesicles may be used for targeting cancer drugs to the malignant tissue. For this purpose we have investigated liposomes which are stable at physiological pH but unstable below pH 6.5 so that the drugs inside of the vesicles may leak out at low pH. Of various compositions studied, the greatest pH sensitivity was found to be with the vesicles composed of PE and palmitic acid (ratio 7:3).
Monomeric ph-sensitive liposomes as drug delivery system are, however, thermodynamically unstable, having relatively short shelf lives. Therefore their use in mechanistic studies and practical application is seriously limited. Thus, we have attempted to obtain pH-sensitive polymeric liposomes as drug carrier system. We have synthesized polymerizable PE which contain a diacetylene group in acyl chains. Upon irradition with ultraviolet-light, DTPE crosslinks via the acetylene groups to produce polymeric vesicles. We are working on the polymeric vesicles to prepare stable polymeric liposome composed of DTPE, PE and palmitic acid which may be used as a cancer drug delivery system targeted to malignant tumor cells.