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閱讀：518 發布時間：2015-4-10
文獻名： Kidney-specific drug delivery system for renal fibrosis based on coordination-driven assembly of catechol-derived chitosan
作者： Hongzhi Qiaoa, Minjie Suna, Zhigui Sua, Ying Xiea, Minglei Chena, Li Zonga, Yahan Gaoa, Huipeng Lia, Jianping Qib, Qun Zhaoc, Xiaochen Gud, Qineng Pinga
a Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China
b Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China
c Department of Pharmaceutics, Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China
d Faculty of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
摘要：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 (re) 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.
關鍵詞：Kidney targeting; Catechol-derived chitosan; Coordination nanocomplex; pH-sensitive; Renal fibrosis