Abstract
Liposomes are artificial phospholipid vesicles consisting of lipid bilayers. They can be used as drug-carriers for drug delivery system (DDS), by entrapping antitumor drugs in the vesicles. We conducted basic experiments and clinical trials of 3 types of DDS using adriamycin (ADM) entrapped in liposomes (Lip-ADM). (1) As the liposomes were prepared from egg yolk phosphatidylcholine, cholesterol and dipalmitoyl phosphatidic acid, Lip-ADM has a character of lymphatic tissue affinity. Gastroendoscopic submucosal injection of Lip-ADM revealed therapeutic lymphnodes delivery of ADM for the treatment of cancer metastases. (2) Liposomes have own liquid-crystalline phase transition temperature(Tc), at which they release entrapped drugs. The temperature-sensitive liposomes encapsulating ADM (TS-Lip-ADM) prepared from dipalmitoylphosphatidylcholine (Tc : 41°C) and cholesterol, showed the temperature-sensitive release of ADM and the enhanced antitumor effect by combination of local hyperthermia of the tumor. (3) Lip-ADM conjugated with anti α-fetoprotein (AFP)monoclonal antibodies showed the selective delivery of ADM and the targeted antitumor effect against AFP-producing xenograft Li-7 in vivo. A possibility of missile therapy using antitumor drugs entrapped in liposomes conjugated with tumor associated monoclonal antibodies was revealed.
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