Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model

Lin, Jia, Shigdar, Sarah, Fang, Ding Zhi, Xiang, Dognxi, Wei, Ming Q., Danks, Andrew, Kong, Lingxue, Li, Lianghong, Qiao, Liang and Duan, Wei 2014, Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model, Plos One, vol. 9, no. 7, e103736, pp. 1-13.

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Title Improved efficacy and reduced toxicity of doxorubicin encapsulated in sulfatide-containing nanoliposome in a glioma model
Author(s) Lin, Jia
Shigdar, Sarah
Fang, Ding Zhi
Xiang, Dognxi
Wei, Ming Q.
Danks, Andrew
Kong, Lingxue
Li, Lianghong
Qiao, Liang
Duan, Wei
Journal name Plos One
Volume number 9
Issue number 7
Season e103736
Start page 1
End page 13
Total pages 13
Publisher Public Library of Science
Place of publication San Francisco, CA
Publication date 2014-07
ISSN 1932-6203
Summary As 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.
Language eng
Field of Research 111504 Pharmaceutical Sciences
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2014, Public Library of Science
Persistent URL http://hdl.handle.net/10536/DRO/DU:30065417

Document type: Journal Article
Collections: School of Medicine
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