Abstract
Aim:
Glioblastoma multiforme is a devastating disease with no curative options due to the difficulty in achieving sufficient quantities of effective chemotherapies into the tumor past the blood-brain barrier. Micelles loaded with temozolomide (TMZ) were designed to increase the delivery of this drug into the brain.
Materials & methods:
pH-responsive micelles composed of distearoyl phosphoethanolamine-PEG-2000-amine and N-palmitoyl homocysteine were surface-functionalized with PDGF peptide and Dylight 680 fluorophore.
Results & conclusion:
PDGF-micelles containing TMZ have specific uptake and increased killing in glial cells compared with untargeted micelles. In vivo studies demonstrated selective accumulation of PDGF-micelles containing TMZ in orthotopic gliomas implanted in mice. Targeted micelle-based drug carrier systems hold potential for delivery of a wide variety of hydrophobic drugs thereby reducing its systemic toxicity.
Keywords:
PDGF; glioblastoma; micelle; nanocarrier; temozolomide.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents, Alkylating / administration & dosage*
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Antineoplastic Agents, Alkylating / pharmacokinetics
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Antineoplastic Agents, Alkylating / therapeutic use
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Brain / drug effects*
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Brain / metabolism
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Brain / pathology
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Brain Neoplasms / drug therapy*
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology
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Cell Line, Tumor
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Dacarbazine / administration & dosage
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Dacarbazine / analogs & derivatives*
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Dacarbazine / pharmacokinetics
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Dacarbazine / therapeutic use
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Delayed-Action Preparations / chemistry
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Delayed-Action Preparations / metabolism*
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Drug Delivery Systems
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Glioblastoma / drug therapy*
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Glioblastoma / metabolism
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Glioblastoma / pathology
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Humans
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Mice, Nude
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Micelles
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Phosphatidylethanolamines / chemistry
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Phosphatidylethanolamines / metabolism
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Protons
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Receptors, Platelet-Derived Growth Factor / chemistry
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Receptors, Platelet-Derived Growth Factor / metabolism*
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Temozolomide
Substances
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Antineoplastic Agents, Alkylating
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Delayed-Action Preparations
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Micelles
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Phosphatidylethanolamines
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Protons
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1,2-distearoylphosphatidylethanolamine
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Dacarbazine
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Receptors, Platelet-Derived Growth Factor
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Temozolomide