壳聚糖论文：新型环糊精固载壳聚糖的合成及其纳米给药系统的研究.doc

壳聚糖论文：新型-环糊精固载壳聚糖的合成及其纳米给药系统的研究【中文摘要】p-环糊精(p-CD)和壳聚糖(CS)都是生物相容性好、可降解的大然高分子材料,已被广泛的应用与药物传递等领域。本课题是新型-环糊精固载壳聚糖(CD-g-NMCS)的合成及其纳米给药系统的研究。首先将p-CD与对甲苯磺酰氯反应得到活化的p-CD衍生物(6-OTs-CD),与CS反应得到了一系列不同环糊精取代度(DSCD=022.86%)的-环糊精固载壳聚糖(CD-g-CS),使用1hNMR, IR,XRD手段表征其结构,采用硫酸-苯酚法测定CD-g-CS的DSCD,通过正交实验优化了CD-g-CS的合成条件。采用DSCD= 14.60%的CD-g-CS进一步马来酸酐酰化,通过控制马来酸酐与CD-g-CS的质量比,得到一系列不同羧基取代度(DSCOOH=030%)的CD-g-NMCS并表征,采用电位滴定法测定CD-g-NMCS的羧基取代度(DSCOOH),考察了CD-g-NMCS新材料的水溶性、粘均分子量和细胞毒性。以CD-g-CS (DSCD= 14.60%), CD-g-NMCS20 (DSCOOH= 20%)和CD-g-NMCS30 (DSCOOH= 30%)为载体材料,以三聚磷酸钠(TPP)为交联剂采用离子凝胶法制备纳米粒,考察了制备纳米粒的条件,在pH=5.0, CD-g-NMCS:TPP= 10:1 (w/w)时制得的纳米粒径为190-280 nm,呈球形,zeta电位为+20-+30 mV。以酮洛芬(KTP)为模型药物,制备了三种包载KTP的CD-g-NMCS纳米粒,具有较高的载药率和包封率。在不同pH (pH=4.0,6.8和7.4)释放介质中考察了载药纳米粒的体外释放特性,实验结果显示在pH 6.8和7.4的释放介质中纳米粒具有一定的缓释释药效果,CD-g-NMCS纳米所用的载体材料的羧基取代度越高其载药纳米粒的体外释药速度越快。CD-g-NMCS纳米粒体外释药具有pH敏感性。CD-g-NMCS在纳米给药领域具有潜在的应用价值。【英文摘要】(3-Cyclodextrin (P-CD) can form inclusion complexes with a variety of drugs, which can increase solubility, improve chemical and physical stability and/or enhance oral absorption of the drug. Chitosan (CS) is used as a bioadhesive polymer since and the CS has non-toxic, biodegradable, biocompatible. mucoadhesion.-CD and CS have been widely used with drug delivery system. In this study, according to the advantages of both CD and CS derivative, we synthesized N-maleoyl chitosan bearing pendant cyclodextrin (CD-g-NMCS) and prepared CD-g-NMCS nanoparticles for drug delivery.In this study, the CD-g-NMCS polymer was synthesized by reacting maleic anhydride and chitosan bearing pendant cyclodextrin. which was prepared with CS and 6-OTs-CD, which was prepared with (3-CD and TsCl. The different-CD substitute degrees (DSCD) of CD-g-CS could be obtained by adjusting mass ratio of 6-OTs-CD to CS, and confirmed by the 1HNMR, IR, XRD. Orthogonal experiments were used to optimize the reaction conditions. The different carboxyl substitute degrees (DSCOOH) of CD-g-NMCS could be obtained by adjusting mass ratio of maleic anhydride to chitosan bearing pendant cyclodextrin (CD-g-CS). CD-g-NMCS was confirmed by the 1HNMR. IR. XRD. The water-solubility, viscosity average molecular weight and cell toxicity of the CD-g-NMCS were examined.CD-g-CS (DSCD= 14.60%). CD-g-NMCS20 (DSCOOH= 21.2%) and CD-g-NMCS30 (DSCOOH= 30.5%) nanoparticles were obtained by ionic gelation method using sodium tripolyphosphate (TPP). which possessed spherical morphology, uniform size (190280 nm), positive electrical charge (+20+30 mV). Entrapment drug studies of the nanoparticles were conducted using ketoprofen (KTP) as a model drug. Various influencing factors in prepartion process were studied, and the drug release tests of the nanoparticles were carried out in vitro using PBS (pH= 4.0.6.8 and 7.4). The in vitro drug release study showed that the KTP-loaded CD-g-NMCS nanoparticles have prolonged release of drug. The in vitro release study indicated CD-g-NMCS nanoparticles had controlled-release effect. The nanoparticles were pH-sensitive. The degree of drug release from KTP-loaded CD-g-NMCS nanoparticles was depended on the DS of CD-g-NMCS. These results found that CD-g-NMCS nanoparticles was a new promising vehicle for controlled release drug.【关键词】壳聚糖 -环糊精 酮洛芬 纳米给药系统【备注】索购全文在线：1.3.99.3.8848 同时提供论文写作一对一指导和论文发表委托服务【英文关键词】Chitosan -Cyclodextrin Ketoprofen Nanoparticles【目录】新型-环糊精固载壳聚糖的合成及其纳米给药系统的研究摘要5-6Abstract6第1章 前言9-181.1 壳聚糖概述9-121.2 环糊精概述12-151.3 环糊精固载壳聚糖的应用15-171.4 立项依据17-18第2章 CD-g-CS的合成18-282.1 引言18-192.2 实验方法19-202.2.1 材料与仪器192.2.2 单-6-对甲苯磺酰-环糊精酯的制备192.2.3 环糊精固载壳聚糖的制备192.2.4 CD-g-CS的表征192.2.5 环糊精取代度和羧基取代度的测定方法19-202.2.6 CD-g-CS反应条件的优化202.3 结果与讨论20-272.3.1 单-6-对甲苯磺酰-环糊精酯的制备20-212.3.2 环糊精固载壳聚糖的制备212.3.3 环糊精固载壳聚糖的表征21-242.3.4 环糊精取代度的测定24-252.3.5 环糊精固载壳聚糖合成条件的优化25-272.4 小结27-28第3章 CD-g-NMCS的合成28-393.1 引言28-293.2 实验方法29-303.2.1 材料与仪器293.2.2 环糊精固载N-马来酰化壳聚糖的制备293.2.3 CD-g-NMCS的表征293.2.4 羧基取代度的测定29-303.2.5 CD-g-NMCS反应条件的优化303.2.6 CD-g-NMCS在不同pH值水溶液中溶解性能的测定303.2.7 CD-g-NMCS相对分子质量的测定303.2.8 CD-g-NMCS细胞毒性的测定303.3 结果与讨论30-383.3.1 环糊精固载N-马来酰化壳聚糖的制备30-313.3.2 CD-g-NMCS的表征31-333.3.3 CD-g-NMCS反应条件的优化33-353.3.4 CD-g-NMCS在不同pH值水溶液中溶解性能的测定353.3.5 相对分子质量的测定35-363.3.6 CD-g-NMCS细胞毒性的测定36-383.4 小结38-39第4章 CD-g-NMCS纳米粒给药系统的研究39-534.1 引言39-404.2 实验方法40-424.2.1 材料与仪器404.2.2 空白CD-g-NMCS纳米粒的制备404.2.3 空白CD-g-NMCS纳米粒在PBS中的稳定性考察40-414.2.4 包载酮洛芬的CD-g-NMCS纳米粒的制备414.2.5 载药纳米粒包封率、载药率的测定414.2.6 包载酮洛芬的CD-g-NMCS纳米粒的体外释放41-424.3 结果