The use of liposomes as carriers of therapeutic agents.
Adriamycin (Doxorubicin) is an important chemotherapeutic agent, but is limited in its clinical usefulness by dose-related cardiomyopathy. Attempts are being made to reduce this toxicity while retaining anti-tumor activity. These include development of chemically modified anthracycline derivatives and coupling of adriamycin to or into macromolecular carriers. We and several other laboratories have shown that entrapment of adriamycin in liposomes (phospholipid vesicles) can reduce toxicity while retaining or, in some cases, enhancing anti-tumor activity. Here we report further results of experiments in mice on toxicity reduction and anti-tumor activity. Approximate maximum tolerated doses (MTD) of adriamycin were determined from normal mouse survival at 240 days after initial treatment. I.V. bolus injection of liposomal-adriamycin was superior to i.v. bolus or i.v. infusion of free drug after a single injection, 5 daily injections or 5 biweekly (every 2 weeks) injections. Using L1210 tumor as a model for systemic leukemia, liposomal adriamycin was as effective as free adriamycin at equal doses, however liposomal-adriamycin was more effective at MTD. M5076 tumor was used as a limited model for comparisons of the effects of liposomal-adriamycin on "primary" and "metastatic" disease. The results showed that whereas free and liposomal adriamycin were without significant effect on "primary", subcutaneous tumor, that liposomal adriamycin, but not free adriamycin had very strong effects on liver "metastases". The results suggest that liposomally administered drugs, including adriamycin, may have utility for treatment of certain types of cancer and for metastases in organs where liposomes accumulate. Where improved anti-tumor activity is coupled with toxicity reduction and simplicity of administration, liposomal administration could be a useful method of drug delivery.
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy; D008081:Liposomes / Q000008:administration & dosage*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL
D008081:Liposomes; D004317:Doxorubicin