Targeted delivery of anticancer drugs with intravenously administered magnetic liposomes in osteosarcoma-bearing hamsters.
Although active targeting of anticancer drugs using magnetically responsive carriers is a very attractive treatment approach for solid tumors, successful results are limited. In particular, the therapeutic utility of intravenously administered magnetically responsive carriers has to date not been clearly established. The present study investigates magnetic liposomes designed to act as anticancer drug carriers, which can be effectively delivered to solid tumors via intravenous administration. Magnetic liposomes with incorporated adriamycin (magnetic ADR liposomes) were prepared by the reverse-phase evaporation method, and an in vivo study was carried out to assess the magnetic targeting of these liposomes to hamster osteosarcoma. The average diameter of liposomes thus prepared was 146 nm. Syrian male hamsters inoculated with osteosarcoma, Os515, in the right hind limb were studied 7 days after inoculation. After the hamsters had received an intravenous administration of either magnetic ADR liposomes or ADR solution (corresponding to 5 mg ADR/kg), the ADR concentrations in plasma, tumor, liver, lung, heart, and kidney were determined at designated time intervals. Administration of magnetic ADR liposomes under magnetic force using a permanent magnet (0.4 tesla) implanted in solid tumor produced an approximately 4-fold higher maximum ADR concentration in the tumor than did administration of ADR solution. The former administration modality induced an increase in ADR concentration in the liver and lung and a decrease in the heart compared with concentrations produced by the latter. The present results indicated that intravenously administered magnetic ADR liposomes can be used to effectively deliver ADR to osteosarcoma implanted with a magnet, as well as to the lung, a common site of metastases for osteosarcoma. Our results also suggest that this new treatment approach, which involves a combination of magnet implantation at the target site and intravenous administration of magnetic liposomes, can improve the clinical chemotherapy of solid tumors.
Kubo
T
T
Department of Orthopaedic Surgery, Faculty of Medicine, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan.
Sugita
T
T
Shimose
S
S
Nitta
Y
Y
Ikuta
Y
Y
Murakami
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D006224:Cricetinae; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers; D008081:Liposomes; D008280:Magnetics; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin