光响应羧甲基壳聚糖纳米囊的制备及研究

发布时间：2018-03-29 01:34

本文选题：羧甲基壳聚糖　切入点：邻硝基苄基　出处：《武汉理工大学》2014年硕士论文

【摘要】：刺激响应性高分子化合物是指在一定条件下，通过其自身物理或者化学性质的改变，对温度、pH等外部刺激作出敏锐应答的物质。与传统的外部刺激相比，光刺激具有其独特的优势，因为外加光的时间、位置和角度都可以进行精确的控制，这样就可以实现对控释体的可控刺激。本文以丁二酸酐作为连接臂，在羧甲基壳聚糖的氨基上接枝具有光响应性的邻硝基苯甲醇，制得光响应羧甲基壳聚糖衍生物，然后进一步制得光响应性的空心纳米囊。主要研究工作和结论如下：一、制备具有光响应性的羧甲基壳聚糖衍生物，确定其结构，研究其相关性质。采用丁二酸酐开环与光响应性的邻硝基苯甲醇反应生成中间产物，然后通过中间产物上的羧基与羧甲基壳聚糖上的氨基反应生成酰胺键得到两亲性羧甲基壳聚糖衍生物，采用红外与核磁手段表征衍生物的结构，通过TLC、UV、HPLC等技术手段考察和确定中间产物和羧甲基壳聚糖衍生物的光响应性。二、以光响应羧甲基壳聚糖衍生物为原料制备空心纳米囊，确定其稳定性、光响应性和pH敏感性。（1）将制备的羧甲基壳聚糖衍生物均匀分散到体系中，经调节pH和超声制得空心纳米囊，然后再戊二醛的辅助交联下得到稳定性较好的空心纳米囊，透射电镜图显示，光响应性空心纳米囊及戊二醛辅助交联后的空心纳米囊都具有很明显的空心结构，并且形态规整，分布均匀，粒径比较均一。与戊二醛辅助交联前的空心纳米囊相比，辅助交联后的空心纳米囊的壳结构更加紧密。（2）动态光散射结果表明，结构经过戊二醛辅助交联锁定的空心纳米囊比未交联的空心纳米囊具有更好的稳定性，并且平均粒径明显变小，分散更加均匀。（3）光响应性空心纳米囊及戊二醛辅助交联后的空心纳米囊都具有较好的光响应性。戊二醛辅助交联的空心纳米囊在光刺激条件下，结构中的光响应基团断裂，壳骨架中的交联网络结构被破坏，，粒径变大，分布变宽；未交联的空心纳米囊在光刺激条件下，结构中的光响应基团断裂，亲疏水比例发生改变，导致疏水作用力的减弱，最终空心纳米囊破裂。（4）戊二醛辅助交联的空心纳米囊显示出明显的pH敏感性。pH值在较低范围时，其粒径较小，而pH值在较高范围时，其粒径较大，但当pH值超过一定范围时，粒径又有变小的趋势；纳米囊中光响应基团的含量对空心纳米囊的pH敏感性影响不大，这是辅助交联剂戊二醛用量相同的原因；当pH＜3.0时，空心纳米囊会沉淀出来，但能够重新分散在合适pH值的溶液中。三、考察以灭草松作为药物模型的载药纳米囊的药物释放释放情况，为该纳米模型在纳米药物载体领域的发展提供理论依据。（1）以所制备的空心纳米囊为载体，以灭草松为药物模型，采用原位包载，得到载药空心纳米囊。投药量影响空心纳米囊的载药量与包封率：随着投药量的增大，载药量也不断增大；但当投药量的增大时，包封率先增大后减小，在一个临界点时达到最大。（2）光刺激环境影响纳米囊的药物释放：在光刺激条件下，药物有较快的释放，而在无光刺激条件下，药物的释放相对缓慢。纳米囊的组成影响纳米囊的药物释放：在暗环境中，三种载药纳米囊的药物释放趋势相同，都没有或是极少量药物释放出来；在光刺激条件下，载药纳米囊中光响应基团的取代度越低，药物释放的速率越快。
[Abstract]:Stimuli responsive polymers is that under certain conditions, through its own physical or chemical properties change of temperature, pH and other external stimuli sensitive response of the material. Compared with the traditional external stimulation, light stimulation has its unique advantages, because the external light time, position and angle can be accurately control, which can be controlled to release to stimulate the body. In this paper, two Ding anhydride as linker in carboxymethyl chitosan grafted with amino light response 2 nitrobenzyl alcohol of the prepared light response of carboxymethyl chitosan derivatives, and then prepared light responsive hollow nano cystic. The research work and conclusions are as follows:
First, the derivatives of carboxymethyl chitosan with light responsiveness are prepared, their structures are determined and their related properties are studied.
The Ding two anhydride ring opening reaction of o-nitrobenzoic methanol formation of intermediate products and the light response, then the two amphiphilic carboxymethyl chitosan derivatives obtained by reaction of carboxyl and amino amide bond of Carboxymethyl Chitosan on the intermediate product, structure, using IR and NMR methods for the characterization of derivatives by TLC, UV, HPLC other technical means to examine and determine the intermediate product and carboxymethyl chitosan derivatives of the light response.
Two, the hollow nanoscale was prepared by light response to carboxymethyl chitosan derivative as raw material, and its stability, light responsiveness and pH sensitivity were determined.
(1) the preparation of carboxymethyl chitosan derivatives were dispersed into the system, by adjusting the pH and ultrasound prepared hollow nanocapsules, auxiliary crosslinking and then glutaraldehyde under hollow nanocapsules better stability, TEM micrographs showed that the optical response of hollow nanocapsules hollow nanocapsules and amyl aldehyde two auxiliary crosslinking after having a hollow structure obviously, and regular shape, uniform distribution of particle size is uniform. Compared with the hollow nanocapsules before the auxiliary crosslinking glutaraldehyde, shell hollow nanocapsules assisted after crosslinking more closely.
(2) the dynamic light scattering results show that the hollow nanocapsules constructed by glutaraldehyde cross-linking and locking are more stable than the uncrosslinked hollow nanocapsules, and the average particle size is smaller and the dispersion is more uniform.
(3) the optical response of hollow nano cystic hollow nano capsule and glutaraldehyde crosslinked auxiliary has better light response. Glutaraldehyde cross-linked hollow nanocapsules in auxiliary light stimulation conditions, structure of the light response group fracture, cross-linked network structure shell is destroyed and the particle size distribution. Wide; non crosslinked hollow nanocapsules in light stimulation conditions, structure of the light response group fracture, hydrophobic ratio change, weaken the hydrophobic force, the final hollow nano capsule rupture.
(4) hollow nanocapsules glutaraldehyde auxiliary crosslinking showed pH sensitivity of.PH obvious value in the lower range, the smaller particle size, and the value of pH in the high range, its larger size, but when the pH value exceeds a certain range, the particle size decreases; nanocapsules in light the response group content on hollow nanocapsules was pH sensitivity, which is why the same auxiliary glutaraldehyde dosage; when pH is less than 3, the hollow nanocapsules will precipitate out of solution, but can be re dispersed in an appropriate pH value.
Three, we investigated the release and release of drug loaded nanocapsules, which provided a theoretical basis for the development of nanocapsules in the field of nanomedicine carriers.
(1) using hollow nanocapsules prepared as the carrier, with bentazone as drug model, obtained by in situ loading, drug loaded nano hollow capsule. The dosage of drug loading and entrapment efficiency of hollow nanocapsules: with the increase of drug dosage, drug loading is increasing constantly; but with the increase of investment the dosage, encapsulation first increases and then decreases, reaches the maximum at a critical point.
(2) light stimulation drug environmental impact nanocapsules release: in light stimulus conditions, drug fast release, but in the absence of light stimulation conditions, the drug release is relatively slow. Effects of nano capsule drug nanocapsules release: in the dark environment, the three kinds of drug loaded nano capsule release the same trend, have no or very little drug release; in light stimulus conditions, the degree of substitution groups lower light response of the drug loaded nano capsule, the rate of drug release more quickly.

【学位授予单位】：武汉理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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