title: Grafting chitosan with polyethylenimine in an ionic liquid for efficient gene delivery.
abstract: Modifying chitosan (CS) with polyethylenimine (PEI) grafts is an effective way to improve its gene transfection performance. However, it is still a challenge to conduct the grafting with fine control and high efficiency, particularly for the modification of water-insoluble CS. Herein, a novel method to graft CS with PEI (1.8 kDa, PEI-1.8) was developed by using ionic liquid 1-butyl-3-methyl imidazolium acetate ([BMIM]Ac) as a reaction solvent, water-insoluble CS as a reaction substrate and 1,1-carbonyldiimidazole (CDI) as a linking agent. The grafting reaction was greatly accelerated and the reaction time was largely shortened to 4 h by taking advantages of the good solubility of CS, the enhanced nucleophilicity of amino groups and the preferential stability of the activated complexes in the ionic liquid. The chitosan-graft-polyethylenimine (CS-g-PEI) products were characterized by 1H NMR, FTIR and GPC. PEI-1.8 was quantitatively grafted to CS through urea linkages, and the grafting degree (GD) was conveniently tuned by varying the molar ratios of PEI-1.8 to D-glucosamine units of CS in the range of 9.0 × 10(-3) to 9.0 × 10(-2). Compared with CS, the synthesized CS-g-PEI copolymers showed higher pDNA-binding affinity, which increased with the GD as shown in Agarose gel electrophoresis. The dynamic light scattering (DLS) experiment demonstrated that the CS-g-PEI/pDNA polyplexes had suitable particle sizes and proper ζ-potentials for cell transfection. The CS-g-PEI copolymer with a medium GD of 4.5% conferred the best gene transfection, with the efficiency 44 times of CS and 38 times of PEI-1.8 in HEp-2 cells. The cytotoxicity of CS-g-PEI was tested and found nearly as low as that of CS and much lower than that of PEI.
authors: State Key Laboratory of Fine Chemicals, Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning, China; Key Laboratory of Biotechnology and Bioresources Utilization-The State Ethnic Affairs Commission-Ministry of Education, College of Life Science, Dalian Nationalities University, Dalian, Liaoning, China.
authors: Huiying
authors: H
authors: Chen
authors: Key Laboratory of Biotechnology and Bioresources Utilization-The State Ethnic Affairs Commission-Ministry of Education, College of Life Science, Dalian Nationalities University, Dalian, Liaoning, China.
authors: Shaohui
authors: S
authors: Cui
authors: State Key Laboratory of Fine Chemicals, Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning, China; Key Laboratory of Biotechnology and Bioresources Utilization-The State Ethnic Affairs Commission-Ministry of Education, College of Life Science, Dalian Nationalities University, Dalian, Liaoning, China.
authors: Yinan
authors: Y
authors: Zhao
authors: State Key Laboratory of Fine Chemicals, Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
authors: Chuanmin
authors: C
authors: Zhang
authors: Key Laboratory of Biotechnology and Bioresources Utilization-The State Ethnic Affairs Commission-Ministry of Education, College of Life Science, Dalian Nationalities University, Dalian, Liaoning, China.
authors: Shubiao
authors: S
authors: Zhang
authors: State Key Laboratory of Fine Chemicals, Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning, China.
authors: Xiaojun
authors: X
authors: Peng
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D004247:DNA / Q000008:administration & dosage*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D052578:Ionic Liquids / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D014162:Transfection
chemical_list: C525963:1-butyl-3-methylimidazolium; D007093:Imidazoles; D052578:Ionic Liquids; C551320:chitosan-graft-polyethylenimine; C006900:N,N-carbonyldiimidazole; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan