title: 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.
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Zhigui
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Minglei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: zong216@yahoo.com.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zong
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Yahan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Huipeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Pharmaceutics, Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0T5, Canada.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: pingqn@cpu.edu.cn.
authors.forename: Qineng
authors.initials: Q
authors.lastname: Ping
mesh_terms: D000818:Animals; D002396:Catechols / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D014018:Tissue Distribution
chemical_list: D002396:Catechols; D004317:Doxorubicin; D048271:Chitosan; C034221:catechol
keywords: Catechol-derived chitosan; Coordination nanocomplex; Kidney targeting; Renal fibrosis; pH-sensitive