使用高脱乙酰度壳聚糖制备了靶向药物载体-叶酸改性壳聚糖微球。首先通过碱法制备了高脱乙酰度的壳聚糖,采用酸碱滴定法和傅里叶变换红外光谱(FTIR)对其结构进行了表征,结果表明,经脱乙酰化处理后的壳聚糖脱乙酰度高达93.8%。然后以高脱乙酰度壳聚糖制备了叶酸改性壳聚糖,创新性地发现用1∶1的二甲基亚砜和水的混合溶剂可以得到壳聚糖和叶酸反应的均相体系。通过不同的改性方案,得到了不同改性程度的壳聚糖,改性程度分别达到了2.60%、5.10%、8.75%和9.49%。最后用三聚磷酸钠交联制备了叶酸改性壳聚糖微球,并用激光粒度仪系统地分析了三聚磷酸钠和改性壳聚糖的用量比例及浓度对微球的粒径、Zeta 电位的影响。研究发现,随着三聚磷酸钠与改性壳聚糖的比值增大,微球的粒径和 Zeta 电位都增大,当比值增加到一定的程度,微球的粒径会快速增加。对三聚磷酸钠和改性壳聚糖加入浓度的研究,发现浓度的增大将导致粒径的增大和Zeta电位的降低。
In this study,chitosan was used for nano-targeted drug carriers preparation.Firstly,highly deacety-lated chitosan was prepared by alkaline process,and evaluated the degree of deacetylation with acid-base titration and FTIR.The results suggested that the degree of deacetylation of chitosan prepared arrived at 93.80%,basically mee-ting the experiment requirements.Then the folic acid modified chitosan was made using the deacetylated chitosan as raw material.The preliminary experiment gave a clue that the water mixed with DMSO at the rate of 1∶1 offered a homogeneous system for the reaction between folic acid and chitosan.After modification process,the different levels of modified chitosan were obtained,and the value achieved 2.60%,5.10%,8.75% and 9.49%,respectively.Final-ly,sodium tripolyphosphate was utilized as a cross-link agent for the further modification of chitosan.After the prepa-ration of the folic acid modified chitosan nanoparticles,the proportion and concentration of sodium tripolyphosphate and modified chitosan were simultaneously studied,focusing on the nanoparticles size and Zeta potential.It was found that with the increasing ratios of sodium tripolyphosphate and modified chitosan,the particle size and Zeta potential of the nanoparticles increased.By studying the influence of sodium tripolyphosphate and the modified chitosan′s concen-tration,we found that the increasing concentration would lead to the enlarging of particle size and declining of Zeta po-tential.
参考文献
[1] | Yoo SH;Lee JS;Park SY;Kim YS;Chang PS;Lee HG.Effects of selective oxidation of chitosan on physical and biological properties[J].International Journal of Biological Macromolecules: Structure, Function and Interactions,20051/2(1/2):27-31. |
[2] | Ong SY;Wu J;Moochhala SM;Tan MH;Lu J.Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties.[J].Biomaterials,200832(32):4323-4332. |
[3] | Chiu, L.L.Y.;Radisic, M..Controlled release of thymosin β4 using collagen-chitosan composite hydrogels promotes epicardial cell migration and angiogenesis[J].Journal of Controlled Release: Official Journal of the Controlled Release Society,20113(3):376-385. |
[4] | 张庆云;张利平;胡迎庆;郭洪声.壳聚糖在靶向制剂中的应用进展[J].天津药学,2004(2):56-58. |
[5] | 蒋新宇;周春山;张俊山.应用三聚磷酸钠为交联剂制备载药物纳米粒的研究[J].中国现代医学杂志,2003(22):69-71. |
[6] | Lu Y;Low PS.Folate-mediated delivery of macromolecular anticancer therapeutic agents.[J].Advanced drug delivery reviews,20025(5):675-693. |
[7] | 欧阳明;丁纯梅;张志国;钱东锋;吴飞.高脱乙酰度壳聚糖的制备[J].安徽化工,2007(2):29-30. |
[8] | 王红昌;孙晓飞.不同分子量高脱乙酰度壳聚糖的制备及表征[J].中国海洋药物,2007(1):16-19. |
[9] | Mansouri S;Cuie Y;Winnik F;Shi Q;Lavigne P;Benderdour M;Beaumont E;Fernandes JC.Characterization of folate-chitosan-DNA nanoparticles for gene therapy[J].Biomaterials,20069(9):2060-2065. |
[10] | 龚金兰;汪森明;胡喜钢;曹漫明;张积仁.肿瘤靶向性药物载体叶酸-壳聚糖微球的制备及特性研究[J].南方医科大学学报,2008(12):2183-2186. |
[11] | 柳时;徐喆;罗智;项光亚.叶酸偶联壳聚糖纳米粒的制备[J].医药导报,2006(6):561-563. |
[12] | 翁优灵;沙爱民.多普勒电泳光散射Zeta电位分析新技术[J].中国测试技术,2005(4):20-23. |
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