溶剂纯化改善聚苯胺纳米材料生物相容性的研究

Research on Improving the Biocompatibility of Polyaniline Nanomaterials Through Solvent Purification

目的考察不同有机溶剂纯化对聚苯胺(polyaniline,PANI)纳米材料生物相容性的影响,为开发新型高分子医用材料奠定基础。方法分别利用二甲基甲酰胺(N,N-dimethylformamide,DMF)和二甲基亚砜(dimethyl sulfoxide,DMSO)对化学氧化法合成的PANI纳米线进行纯化处理,比较纯化前后材料的微观形态变化;将纯化前后的PANI材料配制成100%、50%、25%、10%、5%和1%的浸提液,以BV2细胞为研究对象,采用CCK-8法测定各浸提液组的细胞存活率;将纯化前后的PANI材料配制成100、80、64、51和41 mg·mL^(-1)的混悬液,通过灌胃给药考察材料对小鼠口服急性毒性及对肝肾的损伤。结果所得材料为直径约20 nm的PANI纳米线,经过纯化后其形貌未发生明显改变。未经纯化的100%PANI浸提液具有很强的细胞毒性,但是随着浓度的降低,其毒性逐渐减弱。经DMF和DMSO纯化后,细胞在其浸提液中的存活率均高于同浓度下未纯化材料(P均<0.01)。PANI材料用DMSO纯化后给药,各组小鼠的体质量增长率高于未纯化材料(P<0.05或P<0.01),其最大耐受量(MTD)>3000 mg·kg^(-1)。解剖后,各组小鼠肾脏无明显变化,但是肝细胞受到不同程度的损伤,材料经纯化后的损伤效应低于未纯化材料。结论溶剂处理是一种简便可行的PANI纳米材料纯化策略,可在提高材料生物相容性的同时维持其形貌不变。

Objective To investigate the purification effect of organic solvent on the biocompatibility of polyaniline nanomaterials and lay the foundation for the development of novel polymer medical materials.Methods Polyaniline nanofibers synthesized by chemical oxidation were purified with dimethylformamide and dimethyl sulfoxide,respectively and the morphology of original and purified materials was compared.The original and purified polyanine extracts with 100%,50%,25%,10%,5%and 1%were prepared and the percentage of cell viability was measured by CCK-8 method taking BV2 cells as the object;The original and purified polyaniline suspension with 10080,64,51 and 41 mg·mL^(-1) were prepared and the acute oral toxicity and the damage to liver and kidney were also investigated by intragastric administration in mice.Results Polyaniline nanofibers with the diameter of 20 nm were synthesized.After purification,the morphology of the nanofibers did not change.The 100%extract of crude polyaniline had strong cytotoxicity,but the toxicity gradually decreased with the decrease of concentration.The survival rate of cells purified using DMF and DMSO was significantly higher compared to unpurified materials(P all<0.01).And the cytotoxicity was lower for DMSO-purified PANI materials than DMF-purified ones,but there was no significant difference between two purified materials.The body weight growth rate of mice treated with DMSO-purified material was higher than that of mice treated with crude material(P<0.05 or P<0.01)and MTD is larger than 3000 mg·kg^(-1) in mice.After dissection,the kidney of mice in each group had no obvious changes,but the hepatocyte injury decreased in mice treated with purified PANI nanofibers.Conclusion Solvent treatment is a simple and feasible purification strategy for polyaniline nanomaterials,which can improve the biocompatibility of the materials and keep the morphology of the materials at the same time.