リポソーム封入シスプラチンの脳腫瘍血管透過性に関する超微形態学的研究

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The anticancer chemotherapeutic agerit cisplatin (cis-diamminedichloroplatinum) has several disadvantages, including extreme nephrotoxity, rapid binding to plasma proteins, and poor penetration into the central nervous system. Liposomes would seem to be suitable as carriers of cisplatin to brain tumors. This ultrastructural study was undertaken to identify the capillary permeability of liposome-encapsulated cisplatin in a rat brain tumor model. Brain tumors were induced transplacentally with a single intravenous dose of 50 mg/kg of ethylnitrosourea (ENU). One ml of liposome-encapsulated cisplatin and ferritin prepared from phosphatidylcholine and cholesterol (molar ratio 7:2) was administered via the carotid artery to rats with ENU-induced brain tumors. The tumor platinum content and that of the contralateral hemisphere were assayed by flameless atomic absorption spectrometry. The presence of ferritin-bearing liposomes was demonstrated by electron microscopy of brain capillary endothelium as well as tumor cells. Thirty minutes after drug administration, the average dry-weight platinum concentrations were 3.98±0.50 μg/g within the intracerebral tumors and 0.72±0.24 μg/g in the contralateral hemispheres. Electron microscopic ultrastructural study, which can distinguish ferritin-bearing liposomes from cell materials, demonstrated the presence of liposomes containing ferritin in both cell surface folds and capillary endothelial cells and also within tumor cells. An enlarged electron micrograph of a liposome with a diameter of approximately 0.2 μm suggested the presence of ferritin molecules in the lamellar structure. Liposome-encapsulated cisplatin is apparently able to pass the blood-brain barrier and should be useful in the chemotherapy of glioma.
日本脳神経外科学会の論文
1989-08-15

リポソーム封入シスプラチンの脳腫瘍血管透過性に関する超微形態学的研究

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