Abstract
Nanoparticles made of poly(butyl cyanoacrylate) (PBCA) or poly(lactic-co-glycolic acid) (PLGA) coated with polysorbate 80 or poloxamer 188 enable the transport of cytostatics such as doxorubicin across the blood-brain barrier (BBB). Following intravenous injection to rats bearing intracranially the very aggressive glioblastoma 101/8 these particles loaded with doxorubicin significantly increased the survival times and led to a complete tumor remission in 20-40% of the animals. Moreover, these particles considerably reduced the dose-limiting cardiotoxicity and also the testicular toxicity of this drug. The drug transport across the BBB by nanoparticles appears to be due to a receptor-mediated interaction with the brain capillary endothelial cells, which is facilitated by certain plasma apolipoproteins adsorbed by nanoparticles in the blood.
MeSH terms
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Animals
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Antibiotics, Antineoplastic / administration & dosage*
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Antibiotics, Antineoplastic / adverse effects
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Blood-Brain Barrier* / drug effects
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Blood-Brain Barrier* / metabolism
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Brain Neoplasms* / diagnosis
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Brain Neoplasms* / therapy
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Capillaries / drug effects
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Capillaries / metabolism
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Cerebrovascular Circulation / drug effects
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Doxorubicin / administration & dosage*
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Doxorubicin / adverse effects
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Drug Carriers*
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Enbucrilate
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Endothelial Cells / drug effects
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Endothelial Cells / metabolism
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Excipients
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Humans
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Lactic Acid
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Nanoparticles*
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Poloxamer
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Polyglycolic Acid
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polysorbates
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Rats
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Surface-Active Agents
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Survival Analysis
Substances
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Antibiotics, Antineoplastic
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Drug Carriers
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Excipients
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Polysorbates
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Surface-Active Agents
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Poloxamer
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polyglycolic Acid
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Lactic Acid
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Doxorubicin
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Enbucrilate