title: Synthesis, characterisation and preliminary investigation of the haemocompatibility of polyethyleneimine-grafted carboxymethyl chitosan for gene delivery.
abstract: The development of safe and efficient gene carriers is the key to the clinical success of gene therapy. In the present study, carboxymethyl chitosan (CMCS) was prepared by chitosan (CS) alkalisation and carboxymethylation reactions. Then polyethyleneimine (PEI) was grafted to the backbone of CMCS by an amidation reaction. The CMCS-PEI copolymer showed strong complexation capability with DNA to form nanoparticles, and achieved lower cytotoxicity and higher transfection efficiency compared with PEI (25 kDa) towards 293T and 3T3 cells. Moreover, the haemocompatibility of the CMCS-PEI copolymer was investigated through the aggregation, morphology and lysis of human red blood cells (RBCs), along with the impact on the clotting function with activated partial thromboplastin time (APTT), prothrombin time (PT) and thromboelastographic (TEG) assays. The results demonstrated that the CMCS-PEI copolymer with a concentration lower than 0.05 mg/mL had little impact on the aggregation, morphology or lysis of RBCs, or on blood coagulation. Therefore, the copolymer may be a strong alternative candidate as an effective and safe non-viral vector.
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China; Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China; Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Mo
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China; Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China; Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China. Electronic address: guorui@jnu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China; Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Jinan University, Guangzhou 510632, China; Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Changyong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou 510632, China.
authors.forename: Seeram
authors.initials: S
authors.lastname: Ramakrishna
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D004587:Electrophoresis, Agar Gel; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D057809:HEK293 Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010314:Partial Thromboplastin Time; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D011517:Prothrombin Time; D013916:Thrombelastography; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; C551320:chitosan-graft-polyethylenimine; D011094:Polyethyleneimine; D048271:Chitosan
keywords: Biocompatibility; Chitosan; Gene carrier; Haemocompatibility; Polyethyleneimine