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Kidney-specific drug delivery system for renal fibrosis based on coordination-driven assembly of catechol-derived chitosan.

Abstract
Renal fibrosis is a common progressive kidney disease, and there is a lack of efficient treatment for the condition. In this study, we designed a kidney-specific nanocomplex by forming coordination-driven assembly from catechol-derived low molecular weight chitosan (HCA-Chi), metal ions and active drug molecules. The coordination activities of various metals and ligands, cytotoxicity, immunogenicity and biodistribution of HCA-Chi were investigated. Autofluorescent doxorubicin (DOX) was selected to fabricate HCA-Chi-Cu-DOX ternary nanocomplex for investigating cellular uptake behavior, transmembrane and targeting properties. The nanodevice demonstrated satisfactory stability under normal physiological conditions and pH-responsive drug release in acidic environments. Uptake of HCA-Chi-Cu-DOX by HK-2 cells was dependent on exposure time, concentration, and temperature, and was inhibited by blockers of megalin receptor. Tissue distribution showed that HCA-Chi-Cu-DOX nanocomplex was specifically accumulated in kidney with a renal relative uptake rate (r(e)) of 25.6. When active anti-fibrosis compound emodin was installed in HCA-Chi-Zn-emodin and intravenously injected to the ureter obstructed mice, obvious attenuation of fibrotic progression was exhibited. It was concluded that HCA-Chi coordination-driven nanocomplex showed special renal targeting capacity and could be utilized to develop drug delivery systems for treating renal fibrosis.
AuthorsHongzhi Qiao, Minjie Sun, Zhigui Su, Ying Xie, Minglei Chen, Li Zong, Yahan Gao, Huipeng Li, Jianping Qi, Qun Zhao, Xiaochen Gu, Qineng Ping
JournalBiomaterials (Biomaterials) Vol. 35 Issue 25 Pg. 7157-71 (Aug 2014) ISSN: 1878-5905 [Electronic] Netherlands
PMID24862442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Catechols
  • Doxorubicin
  • Chitosan
  • catechol
Topics
  • Animals
  • Catechols (chemistry, pharmacokinetics)
  • Cell Line, Tumor
  • Chitosan (chemistry, pharmacokinetics)
  • Doxorubicin (chemistry, pharmacokinetics)
  • Drug Delivery Systems (methods)
  • Fibrosis
  • Humans
  • Kidney (drug effects, pathology)
  • Kidney Diseases (drug therapy)
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microscopy, Confocal
  • Molecular Weight
  • Nanoparticles (chemistry)
  • Rats
  • Tissue Distribution

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