聚乙二醇复合物论文：新型纳米制剂的研究—碳纳米管作为药物载体的分散特性.docVIP

聚乙二醇复合物论文：新型纳米制剂的研究—碳纳米管作为药物载体的分散特性 【中文摘要】碳纳米管作为药物传递系统的载体,具有较大的比表面积,可装载从小分子到蛋白质等不同分子量大小的物质；沿着纳米管轴向有较高的长径比,为不同改性基团提供了多个吸附位点；且碳纳米管可进入细胞核内。但是,碳纳米管不溶于水以及有机溶剂,因此碳纳米管的分散成为其应用的首先需要解决的问题。本论文分别以胆固醇、叶酸接枝聚乙二醇制备能分散碳纳米管的聚合物,考察对碳纳米管的分散效果,并以小檗碱为模型药物,研究碳纳米管作为药物载体的分散性质。论文首先制备了胆固醇聚乙二醇单甲醚和叶酸聚乙二醇复合物,并经红外光谱和1HNMR表征。考察了不同反应溶剂、温度对丁二酸单胆固醇酯收率的影响,进一步合成胆固醇聚乙二醇单甲醚,并测定了不同反应时间对叶酸聚乙二醇复合物中叶酸取代度的影响。以吐温80、TPGS、Cremophor、胆固醇聚乙二醇单甲醚、叶酸聚乙二醇复合物作为改性剂,研究五种改性剂对单壁碳纳米管(SWNT)以及多壁碳纳米管(MWNT)的分散性,对分散于溶液中的两种碳纳米管的量进行测定。比较了不同CNTs与改性剂的质量比对分散率的影响,并对分散后的CNTs水溶液稳定性进行研究。以小檗碱为模型药物,实验不同条件(温度、pH值、药物加入量)对吸附药量的影响,并考察载药碳纳米管在pH=5.5和6.8缓冲液中的体外释放情况。实验结果表明,经胆固醇聚乙二醇单甲醚改性的CNTs能以较高的浓度(MWNT的浓度达到230μg/mL; SWNT的浓度达到50μg/mL; CNTs/改性剂=1：8)稳定地分散于水溶液中,明显高于短链非离子表面活性剂对CNTs的分散性。以小檗碱为模型药物,筛选出的最佳载药条件为4℃,pH=9.0,其中SWNT的载药比能达到5.5。五种改性剂的使用对CNTs的相对载药量(以吸附药量与分散的CNTs的量之比表示)影响较小,但相同体积的溶液中,以胆固醇聚乙二醇单甲醚为改性剂时,SWNT绝对载药量(以吸附药量与CNTs的加入量之比表示)提高了约41.8%, MWNT绝对载药量提高约9.1%。小檗碱在pH=5.5的微酸性环境下的释放明显高于中性环境,为碳纳米管作为肿瘤靶向载药系统研究提供了参考。 【英文摘要】Carbon nanotubes(CNTs), as the potential carrier of nano-materials, had large specific surface areas that could be filled with the desired molecules, ranging from small molecules to proteins. It aslo had a high aspect ratio which provided multiple attachment sites for various functionalization groups. It was readily taken up by Cells and could reach the cell nuclei. However, the sidewall of CNTs was hydrophobic, which made CNTs uridissolved in water and organic solvents. The dispersion of CNTs was an essential precondition of their application. The purpose of the study was to obtain water-solubility CNTs used as a novel tumor targeted nano-carrier by combining the advantages of hydrophilic PEG derivatives with folic acid cholesterol. The Cholesterol-PEG and FA-PEG polymers were synthesized to modificate CNTs and other surfactants were used as comparison. Berberine was selected as model drug to evaluate the properbility of CNTs as drug carriers.The effects of different reaction solvents and temperature on the yield of Monocholesterylsucc