[Selective hepatic arterial infusion of liposomes containing antitumor agents]

To improve the targeting effect in cancer chemotherapy, liposomes containing Adriamycin (Lip-ADM) and monoclonal antibody-conjugated Lip-ADM (Lip-ADM = Ab) were prepared and examined experimentally and clinically. The liposomes used as biodegradable drug carriers, were prepared from a lipid mixture of egg yolk phosphatidylcholine, cholesterol and dipalmitoyl phosphatidic acid and Adriamycin (ADM) solution was added to prepare multilamellar vesicles (MLV). Small unilamellar vesicles (SUV) were prepared from MLV by sonication and monoclonal antibodies were conjugated to SUV by the SPDP method. Experimentally, antigen-specific acceleration of in vitro and in vivo anti-tumor effects was observed. As a high tissue distribution of Lip-ADM in the liver was observed and as sinusoidal capillaries, which are found in the liver, were expected to allow penetration of liposomes through the relatively large gaps in the endothelium into the underlying organ parenchymal cells, clinical application of Lip-ADM was started for patients with hepatic metastasis of gastrointestinal cancer by selective hepatic arterial infusion. Ten patients were treated by Lip-ADM which was administered at 8-30 mg/body cumulatively. No serious adverse reaction was observed except slight fever and leukocytopenia. The preliminary evaluation of anti-tumor effects on hepatic metastasis was LPR, 1MR, 6NC and 1PD. Repeat administrations of Lip-ADM or Lip-ADM = Ab using a retained infusion catheter and silicone reservoir were started in order to improve the more accelerated clinical effects.