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Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model
journal contribution
posted on 2014-07-01, 00:00 authored by Jia Lin, Sarah ShigdarSarah Shigdar, D Fang, Dongxi Xiang, M Wei, A Danks, Lingxue KongLingxue Kong, L Li, L Qiao, Wei DuanWei DuanAs a glycosphingolipid that can bind to several extracellular matrix proteins, sulfatide has the potential to become an effective targeting agent for tumors overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting toxicity of doxorubicin (DOX), a sulfatide-containing nanoliposome (SCN) encapsulation approach was employed to improve treatment efficacy and reduce side effects of free DOX. This study analysed in vitro characteristics of sulfatidecontaining nanoliposomal DOX (SCN-DOX) and assessed its cytotoxicity in vitro, as well as biodistribution, therapeutic efficacy, and systemic toxicity in a human glioblastoma U-118MG xenograft model. SCN-DOX was shown to achieve highest drug to lipid ratio (0.5:1) and a remarkable in vitro stability. Moreover, DOX encapsulated in SCN was shown to be delivered into the nuclei and displayed prolonged retention over free DOX in U-118MG cells. This simple two-lipid SCN- DOX nanodrug has favourable pharmacokinetic attributes in terms of prolonged circulation time, reduced volume of distribution and enhanced bioavailability in healthy rats. As a result of the improved biodistribution, an enhanced treatment efficacy of SCNDOX was found in glioma-bearing mice compared to the free drug. Finally, a reduction in the accumulation of DOX in the drug’s principal toxicity organs achieved by SCN-DOX led to the diminished systemic toxicity as evident from the plasma biochemical analyses. Thus, SCN has the potential to be an effective and safer nano-carrier for targeted delivery of therapeutic agents to tumors with elevated expression of tenascin-C in their microenvironment.
History
Journal
Plos OneVolume
9Issue
7Season
e103736Pagination
1 - 13Publisher
Public Library of ScienceLocation
San Francisco, CAPublisher DOI
ISSN
1932-6203Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2014, Public Library of ScienceUsage metrics
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