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URL Address
<a href="http://doi.org/10.1166/jbn.2013.1598" target="_blank" rel="noreferrer noopener">http://doi.org/10.1166/jbn.2013.1598</a>
Pages
1029–1040
Issue
6
Volume
9
Dublin Core
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Title
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Antitumor efficacy and tolerability of systemically administered gallium acetylacetonate-loaded gelucire-stabilized nanoparticles.
Publisher
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Journal of biomedical nanotechnology
Date
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2013
2013-06
Subject
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*Lethal Dose 50; Adenocarcinoma/*drug therapy/pathology; Animals; Antineoplastic Agents/administration & dosage/pharmacokinetics/toxicity; Cell Line; Dose-Response Relationship; Drug; Drug Stability; Drug Tolerance; Gallium/*administration & dosage/pharmacokinetics/*toxicity; Humans; Metabolic Clearance Rate; Mice; Nanocapsules/*administration & dosage/chemistry/*toxicity; Nude; Organ Specificity; Tissue Distribution; Treatment Outcome; Triglycerides/chemistry; Tumor
Creator
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Wehrung Daniel; Bi Lipeng; Geldenhuys Werner J; Oyewumi Moses O
Description
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The widespread clinical success with most gallium compounds in cancer therapy is markedly hampered by lack of tumor specific accumulation, poor tumor permeability and undesirable toxicity to healthy tissues. The aim of this work was to investigate for the first time antitumor mechanism of a new gallium compound (gallium acetylacetonate; GaAcAc) while assessing effectiveness of gelucire-stabilized nanoparticles (NPs) for potential application in gallium-based lung cancer therapy. NPs loaded with GaAcAc (Ga-NPs) were prepared using mixtures of cetyl alcohol with Gelucire 44/14 (Ga-NP-1) or Gelucire 53/13 (Ga-NP-2) as matrix materials. Of special note from this work is the direct evidence of involvement of microtubule disruption in antitumor effects of GaAcAc on human lung adenocarcinoma (A549). In-vivo tolerability studies were based on plasma ALT, creatinine levels and histopathological examination of tissues. The superior in-vivo antitumor efficacy of Ga-NPs over GaAcAc was depicted in marked reduction of tumor weight and tumor volume as well as histological assessment of excised tumors. Compared to free GaAcAc, Ga-NPs showed a 3-fold increase in tumor-to-blood gallium concentrations with minimized overall exposure to healthy tissues. Overall, enhancement of antitumor effects of GaAcAc by gelucire-stabilized NPs coupled with reduced exposure of healthy tissues to gallium would likely ensure desired therapeutic outcomes and safety of gallium-based cancer treatment.
Identifier
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<a href="http://doi.org/10.1166/jbn.2013.1598" target="_blank" rel="noreferrer noopener">10.1166/jbn.2013.1598</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Lethal Dose 50
2013
Adenocarcinoma/*drug therapy/pathology
Animals
Antineoplastic Agents/administration & dosage/pharmacokinetics/toxicity
Bi Lipeng
Cell Line
Department of Pharmaceutical Sciences
Dose-Response Relationship
Drug
Drug Stability
Drug Tolerance
Gallium/*administration & dosage/pharmacokinetics/*toxicity
Geldenhuys Werner J
Humans
Journal of biomedical nanotechnology
Metabolic Clearance Rate
Mice
Nanocapsules/*administration & dosage/chemistry/*toxicity
NEOMED College of Pharmacy
Nude
Organ Specificity
Oyewumi Moses O
Tissue Distribution
Treatment Outcome
Triglycerides/chemistry
Tumor
Wehrung Daniel