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壳聚糖接枝聚丙交酯共聚物的制备、血液凝固及细胞相容性评价

Preparation, blood coagulation and cell compatibility evaluation of chitosan-graft-polylactide copolymers.

作者信息

Wang Qi, Liu Pei, Liu Peifeng, Gong Tao, Li Suming, Duan Yourong, Zhang Zhirong

机构信息

Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, People's Republic of China.

出版信息

Biomed Mater. 2014 Feb;9(1):015007. doi: 10.1088/1748-6041/9/1/015007. Epub 2014 Jan 21.

Abstract

Biodegradable chitosan-graft-polylactide (PLA-CS) copolymers were prepared by the grafting of a poly(L-lactide) (PLLA) or poly(D-lactide) (PDLA) precursor to the backbone of chitosan using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC ⋅ HCl) and N-hydroxysuccinimide (NHS) as a coupling agent. The blood and cell compatibility of the graft copolymers were investigated in comparison to PLLA and PDLA homopolymers. The coagulation properties of PLA-CS were evaluated by hemolysis, plasma recalcification, dynamic blood clotting and protein absorption assays. PLA-CS copolymers present similar hemolysis ratio and plasma recalcification time as PLA, but slower dynamic blood clotting and lower protein absorption. The cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), agar diffusion and lactate dehydrogenase (LDH) experiments. All the samples presented no effect on the viability to cells. Inflammatory cytokine analysis using sandwich ELISAs revealed that PLA-CS would not stimulate inflammatory activity.

摘要

使用1-乙基-3-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC·HCl)和N-羟基琥珀酰亚胺(NHS)作为偶联剂,通过将聚(L-丙交酯)(PLLA)或聚(D-丙交酯)(PDLA)前体接枝到壳聚糖主链上,制备了可生物降解的壳聚糖-接枝-聚丙交酯(PLA-CS)共聚物。与PLLA和PDLA均聚物相比,研究了接枝共聚物的血液和细胞相容性。通过溶血、血浆复钙、动态血液凝固和蛋白质吸收试验评估了PLA-CS的凝血性能。PLA-CS共聚物的溶血率和血浆复钙时间与PLA相似,但动态血液凝固较慢,蛋白质吸收较低。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)、琼脂扩散和乳酸脱氢酶(LDH)实验评估细胞活力。所有样品对细胞活力均无影响。使用夹心酶联免疫吸附测定法进行的炎性细胞因子分析表明,PLA-CS不会刺激炎性活性。

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