[Ultrastructural study of capillary permeability of liposome-encapsulated cisplatin in an experimental rat brain tumor model].

The anticancer chemotherapeutic agent cisplatin (cis-diamminedichloroplatinum) has several disadvantages, including extreme nephrotoxicity, 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 micrograms/g within the intracerebral tumors and 0.72 +/- 0.24 micrograms/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 micron 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.