基于瞬时纳米沉淀法可控制备载药纳米粒子

发布时间：2018-01-30 04:07

本文关键词： 瞬时纳米沉淀法载药纳米粒子 mPEG-b-PCL β-胡萝卜素　出处：《华东理工大学》2017年硕士论文　论文类型：学位论文

【摘要】：瞬时纳米沉淀(Flashnanoprecipitation,FNP)技术,是一种可以在极短时间内制备包含有机活性物质的聚合物纳米粒子的新型技术。与传统的透析法制备纳米粒子相比,FNP技术的优势在于其大大缩短了纳米粒子的制备时间,整个制备流程在几秒内即可完成。近年来利用FNP技术制备纳米粒子得到了越来越多的关注。本文旨在通过两亲性嵌段共聚物甲氧基聚乙二醇-b-聚己内酯(mPEG-b-PCL)的制备和对模型药物β-胡萝卜素的包裹,对利用FNP技术制备载药纳米粒子进行进一步的基础研究。在聚合物mPEG-3-PCL中,mPEG、PCL均具有良好的生物相容性,且PCL具有很好的生物降解性,可以被广泛运用于载药领域。本文合成了一系列具有不同分子量及不同分子结构的两亲性嵌段聚合物,并用核磁共振氢谱、凝胶渗透色谱测定了其分子量,利用荧光分光光度计测试了其临界胶束浓度。随后,以β-胡萝卜素作为模型药物,利用FNP技术制备了一系列包裹有β-胡萝卜素的纳米粒子。通过改变两亲性共聚物的结构、分子量、浓度及溶剂比(H20/THF)成功实现了对纳米粒子尺寸的调控。实验结果表明:在实验研究范围内,聚合物亲水部分比例增大,纳米粒子尺寸减小;亲水部分比例相同时,分子量越大,纳米粒子尺寸越小;当聚合物浓度较高时(1Og/L),制备的纳米粒子粒径分布更窄,粒子更稳定。另外,本文也对利用FNP技术制备三嵌段聚合物载药纳米粒子进行了初步探索,但是由于其稳定性较差,其构效关系有待进一步深入研究。最后,本文对比了利用传统的透析法与FNP技术制备载药纳米粒子,实验结果表明:在实验研究范围内,当聚合物相同时,利用FNP技术制备得到的载药纳米粒子的包封率及载药率均高于传统法制备的纳米粒子,且前者的制备时间短,效率高。通过以上研究,本文成功实现了利用FNP技术制备尺寸可调控二嵌段载药聚合物纳米粒子,为FNP技术的进一步研究和应用奠定了相关的工作基础。
[Abstract]:Flashnanoprecipitation-FNPs technique for transient nanoprecipitation. It is a new technology to prepare polymer nanoparticles containing organic active substances in a very short time, compared with the traditional dialysis method. The advantage of FNP technology is that it shortens the preparation time of nanoparticles. The whole preparation process can be completed in a few seconds. In recent years, more and more attention has been paid to the preparation of nanoparticles using FNP technology. The aim of this paper is to use amphiphilic block copolymer methoxy polyethylene glycol-b-polycaprolactone. (. Preparation of mPEG-b-PCL and encapsulation of model drug 尾 -carotene. The preparation of drug loaded nanoparticles by FNP technology was further studied. All of them have good biocompatibility in polymer mPEG-3-PCL. PCL has good biodegradability and can be widely used in the field of drug loading. A series of amphiphilic block polymers with different molecular weight and molecular structure were synthesized and used in nuclear magnetic resonance spectroscopy (NMR). The molecular weight was determined by gel permeation chromatography, the critical micelle concentration was measured by fluorescence spectrophotometer, and then 尾 -carotene was used as the model drug. A series of nanoparticles coated with 尾 -carotene were prepared by FNP technique. The molecular weight of the amphiphilic copolymers was changed by changing the structure of the copolymers. The concentration and solvent ratio of H20 / THFs have successfully controlled the size of nanoparticles. The experimental results show that in the range of experimental study, the proportion of hydrophilic part of polymer increases and the size of nanoparticles decreases. When the proportion of hydrophilic part is the same, the larger the molecular weight, the smaller the size of nanoparticles. When the polymer concentration is higher, the particle size distribution is narrower and the particle size is more stable. In this paper, the preparation of triblock polymer drug-loaded nanoparticles using FNP technology was also explored, but because of its poor stability, its structure-activity relationship needs to be further studied. Finally. In this paper, the preparation of drug loaded nanoparticles by traditional dialysis method and FNP technology is compared. The experimental results show that: in the range of experimental study, when the polymer is the same. The encapsulation efficiency and drug loading rate of the drug loaded nanoparticles prepared by FNP technology are higher than those of the traditional method, and the preparation time of the former is short and the efficiency is high. In this paper, the preparation of diblock drug loaded polymer nanoparticles by FNP has been successfully realized, which lays a foundation for the further research and application of FNP technology.
【学位授予单位】：华东理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.1;TB383.1

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