Liposomes as Carriers of Cisplatin into the Central Nervous System : Experiments with 9L Gliomas in Rats

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The anticancer agent cis-diamminedichloroplatinum (cisplatin) has several disadvantages, including extreme nephrotoxity, rapid binding to plasma proteins, and poor penetration of the central nervous system. In this study liposomes, which can cross the blood-brain barrier, were investigated for their potential in delivering therapeutic agents to brain tumors. Liposomes prepared from egg phosphatidylcholine and cholesterol in a 3 : 1 molar ratio were divided into 1-ml aliquots and either labeled with ^<14>C or treated with horseradish peroxidase (HRP). The preparations were administered via the carotid artery to rats bearing 9L glioma. Radioactive uptake by brain tumor and normal tissues was measured with a liquid scintillation counter. The presence of HRP-containing liposomes in capillary endothelium and brain tumor cells was demonstrated by light and electron microscopic histochemical techniques. Thirty minutes after injection of ^<14>C-labeled liposomes, radioactive uptake was higher in the spleen than in normal brain, brain tumor, liver, and kidney. Also uptake was greater in brain tumor and lower in kidney than that of cisplatin given alone. Light microscopy showed HRP-containing liposomes in brain tumor tissue 30 minutes after injection. On electron microscopy, liposomes were found to be regularly distributed in surface invaginations and vesicles of capillary endothelial cells. They were also observed within tumor cells. These results indicate that liposomes can penetrate the blood-brain barrier and hold promise as drug carriers in the treatment of brain tumors with cisplatin.
日本脳神経外科学会の論文
1990-04-15

Liposomes as Carriers of Cisplatin into the Central Nervous System : Experiments with 9L Gliomas in Rats

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