New drug delivery system for brain tumor chemotherapy using 40.DEG.C.-adriamycin thermosensitive liposome

Because the cytotoxic effect of hyperthermia in the 42-43°C range has been demonstrated, a transition temperature of the conventional liposomes have so far been 42°C to enhance the synergistic effect of hyperthermia and antitumor drugs. When considered this drug delivery system as clinical use, an important problem about this treatment is that the glioma cells invade wide portions of the brain and present technology has not yet been able to achieve the heating of the wide areas invaded by glioma cells. On the other hand, it has been remarked that the blood brain barrier(BBB) limits the ability of many antitumor drugs to penetrate the central nervous system. Despite of their greater cytotoxic effects on glioma cells in vitro, many drugs, such as adriamycin (ADM), have not so far been used mainly because they are regarded as being blocked by the BBB. In order overcome these roblems we prepared liposomes which brought a sharp release rate of ADM above 40°C. This liposome showed a significantly great antitumor effect against rat malignant gliomas which were transplanted into their legs at the temperature of 40°C. These results suggests that this procedure (1) contributes to the synergistic effect of hyperthermia and antitumor drugs in the regions heated above 42°C, (2) helps to deliver the antitumor drugs more widely with the temperature of 40°C, (3) gives a good chance to many antitumor drugs which have so far not been used from the problem of the BBB. We suggest that this advantage of our plan could outweigh the disadvantages of the conventional thermo-chemotherapy.