Arrest and retention of multilamellar liposomes in the brain of normal mice or mice bearing experimental brain metastases.
The blood-brain barrier presents a major obstacle to the systemic treatment of malignant brain tumors and brain metastases. We investigated whether the direct injection of liposomes into the internal carotid artery of normal mice or mice with experimental brain-melanoma metastases could allow delivery of anticancer drugs across this barrier. Liposomes of different sizes (greater than 5 microns, less than 1 micron, 40-80 nm) and lipid compositions were injected i.v. or into the internal carotid artery. The retention of liposomes in the brain of normal C3H/HeN mice was similar to that observed in mice with experimental brain cancer metastasis. The highest accumulation of liposomes in the brain occurred with large multilamellar vesicles, which also produced severe toxicity presumably due to embolism. Smaller liposomes were not toxic but did not accumulate in the brain. Liposomes injected i.v. did not accumulate in the brain, either. Thus, neither i.v. nor intracarotid administration of liposomes produce results suitable for therapy of brain tumors/metastases.
Department of Cell Biology, The University of Texas M.D. Anderson Cancer Center, Houston.
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Schackert
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Fan
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Nayar
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Fidler
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000556:secondary; D005260:Female; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008081:Liposomes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000556:secondary; D051379:Mice; D009368:Neoplasm Transplantation
D007457:Iodine Radioisotopes; D008081:Liposomes