壳聚糖论文新型β-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β-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β-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-β-CD),与CS反应得到了一系列不同环糊精取代度(DSCD=0～22.86%)的β-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=0～30%)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.β-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-β-CD, which was prepared with (3-CD and TsCl. The differentβ-CD substitute degrees (DSCD) of CD-g-CS could be obtained by adjusting mass ratio of 6-OTs-β-CD to CS, and confirmed by the 1HNMR, IR, XRD. Orthogonal experiments were used to optimize the reaction conditions. The different carboxyl substitute degr