壳聚糖修饰的PLGA纳米粒作为蛋白多肽类药物载体的研究  

The study of PLGA nanoparticle surface modified with chitosan as protein drug carriers

作　　者：陈红丽[1] 吕洁丽[2] 晏杰 王银松[4] 郭伟云[1] 丰慧根[1] 陈汉 张其清 

机构地区：[1]新乡医学院生命科学技术系,河南省遗传性疾病与分子靶向药物重点实验室培育基地,河南新乡453003 [2]新乡医学院药学院,河南新乡453003 [3]中国医学科学院&协和医学院生物医学工程研究所,天津300192 [4]天津医科大学药学院,天津300070

出　　处：《功能材料》2011年第2期202-205,共4页Journal of Functional Materials

基　　金：国家重大科学研究计划资助项目(2006CB933300);新乡医学院省级重点学科开放课题资助项目(ZD200944)

摘　　要：采用溶剂挥发法,以乳酸羟基乙酸共聚物(PLGA)制备了载牛血清白蛋白(BSA)的PLGA纳米粒(PLGA NP),采用两种修饰方式(直接吸附法和共价交联法)以壳聚糖(chitosan,CS)修饰纳米粒表面,通过考察修饰方法对纳米粒的理化性质、释药性质以及对BSA构型的影响,吸附法修饰的纳米粒(ADCSNP)包封率提高,达到(87.8±3.1)%,突释效应显著;共价交联法修饰的纳米粒(CBCS NP)包封率降低,释药速率增加。3组纳米粒释放速率顺序为V(CBCSNP)>V(ADCS NP)>V(PLGA NP)。PLGA NP与ADCS NP包载的BSA构象未见明显改变,而CBCSNP包载的BSA的圆二色谱中α-螺旋含量降低,β-折叠增加。因此,ADCS NP更适合作为蛋白多肽类药物载体。The purpose of this research was to develop polylactic-co-glycolic acid nanoparticles（PLGA NP） surface modified with chitosan（CS）.PLGA NP were prepared by a solvent evaporation technique.The PLGA NP surface was modified with CS by two strategies（adsorption and covalent binding,ADCS NP,CBCS NP）.The change of zeta potential,encapsulation efficiency,drug loading and in vitro release of nanoparticles were investigated using bovine serum albumin（BSA） as a model drug.PLGA NP of（228.1±20.4）nm in diameter characterized by the laser light scattering technique,SEM are spherical and its drug encapsulation efficiency is（84.1±3.4）%.Zeta potential of PLGA NP was measured to be negative-（23.31±3.15）mV.The positive zeta potential of modified nanoparticles reveals the presence of CS on the surface of the modified nanoparticles.X-ray photoelectron spectroscopy（XPS） shows the N1s（atomic orbital 1s of nitrogen） region of the surface of the modified nanoparticles,corresponding to the primary amide of CS.In vitro drug release demonstrated that the release ratios of BSA from three kinds nanoparticles followed the order of V（CBCS NP）V（ADCS NP）V（PLGA NP）.The conformation of BSA from the CBCS NP was altered（CD data） with the reductions of α-helices,and with increases of β-sheet for free BSA.The conformations of the BSA from PLGA NP and ADCS NP did not underwent significant changes.ADCS NP showed a potential as a good carrier for the pepteids drugs.

关 键 词：PLGA纳米粒 壳聚糖 BSA 修饰 圆二色谱 

分 类 号：O636.1[理学—高分子化学]