pH敏感性两性壳聚糖/聚乙烯亚胺复合纳米粒的制备及其性能研究Preparation of pH Sensitive CEC/PEI Complex Nanoparticles and Investigation of Its Characteristics
赵倩,薛荣,张毅,韩晓燕
ZHAO Qian,XUE Rong,ZHANG Yi,HAN Xiaoyan
摘要(Abstract)：
目的制备pH敏感性两性壳聚糖/聚乙烯亚胺(CEC/PEI)复合纳米粒,并检测其性能。方法壳聚糖和丙烯酸经过迈克尔加成反应得到可直接溶于水的两性壳聚糖CEC,再与PEI一定条件下自组装形成具有pH敏感性的CEC/PEI大分子复合纳米粒。通过红外、核磁对CEC结构进行表征,浊度法考察CEC的pH敏感性及CEC/PEI复合纳米粒的形成。以混合法包载盐酸阿霉素,并对其体外释药行为进行考察。结果复合纳米粒包载盐酸阿霉素载药量可达10.45%,包封率为15.53%,缓释效果明显。结论 CEC/PEI复合纳米粒有良好的pH敏感性,对盐酸阿霉素具有一定包载能力,体外释放具有明显的缓释作用。
OBJECTIVE To prepare pH sensitive CEC/PEI complex nanoparticles and their characteristics were investigated.METHODS N-carboxymethyl chitosan is synthesized by the Michael addition reaction of succinic anhydride and primary amines of chitosan. Its structure was characterized by IR and NMR. The pH sensitivity of CEC was elucidated by turbidity method. A stable CEC/PEI complex nanoparticles were formed at pH 7. 4 by electrostatic interaction,where the PEI dendrimer surface was covered with CEC,as demonstrated by turbidity method. Doxorubicin hydrochloride was loaded in CEC/PEI complex nanoparticles by mixing method. The encapsulation efficiency and drug loading efficiency were determined by UV. The in vitro release characteristics of drug-loaded complex nanoparticles were investigated.RESULTS The encapsulation efficiency and drug loading efficiency of doxorubicin hydrochloride were15. 53% and 10. 45%, respectively. The release of drug-loaded complex nanoparticles in vitro showed sustained characteristics.CONCLUSION Experimental results show that the CEC/PEI complex nanoparticles have pH sensitivity and have a certain capacity of loading doxorubicin hydrochloride. The CEC/PEI complex nanoparticles are prospective drug delivery carrier for tumor delivery system.
关键词(KeyWords)：
pH敏感性;两性壳聚糖;聚乙烯亚胺;复合纳米粒
pH sensibility;N-carboxymethyl chitosan;PEI;complex nanoparticles
基金项目(Foundation): 国家自然科学基金(81202921)
作者(Author):
赵倩,薛荣,张毅,韩晓燕
ZHAO Qian,XUE Rong,ZHANG Yi,HAN Xiaoyan
参考文献(References)：
- [1]Gullotti E,Yeo Y.Extracellularly Activated Nanocarriers:A New Paradigm of Tumor Targeted Drug Delivery[J].Mol Pharrnaceut,2009;6(4):1041-1051.
- [2]杨扬,佘汶川,罗奎,等.基于聚合物的环境敏感型纳米抗肿瘤药物传输系统的研究[J].生物化学与生物物理进展,2013,10:1039-1048.
- [3]Liu D,Hu H,Zhang J,et al.Drug p H-Sensitive Release in vitro and Targeting Ability of Polyamidoamine Dendrimer Complexes for Tumor Cells[J].Chemical&Pharmaceutical Bulletin,2011,59(1):63-71.
- [4]Liu KC,Yeo Y.Zwitterionic Chitosan-Polyamidoamine Dendrimer Complex Nanoparticles as a p H-Sensitive Drug Carrier[J].Mol Pharmaceutics,2013,10(5):1695-1704.
- [5]蔡洪.海藻酸钠复合物纳米胶束的制备及性能研究[D].江南大学,2012.
- [6]Kurita Y,Isogai A.N-Alkylations of chitosan promoted with sodium hydrogen carbonate under aqueous conditions[J].International Journal of Biological Macromolecules,2012,50(3):741-746.
- [7]Warayuth Sajomsang,Pattarapond Gonil,Supawan Tantayanon Antibacterial activity of quaternary ammonium chitosan containing mono or disaccharide moieties:Preparation and characterization[J].International Journal of Biological Macromolecules,2009,44(5):419-427.
- [8]于娜娜,王笃政.壳聚糖改性最新研究进展[J].精细与专用化学品,2011,06:43-48.
- [9]郝英魁,杨学东.载药壳聚糖纳米粒的研究进展[J].中国药学杂志,2005,17:1292-1295.
- [10]李经忠,王青青.新型非病毒载体聚乙烯亚胺体内应用的研究进展[J].国外医学.药学分册,2004,01:34-37.
- [11]王艳波.新型PEI衍生物材料的合成及在肿瘤基因递送中的应用研究[D].吉林大学,2014.
- [12]Xu P,Bajaj G,Shugg T.Zwitterionic chitosan derivatives for p H-sensitive stealth coating.[J].Biomacromolecules,2010,11(9):2352-2358.
- [13]郑永丽.壳聚糖基聚电解质复合物纳米粒子的制备、表征及其药物负载性能的初步研究[D].复旦大学,2006.