基于微流控技术的药物缓释研究

发布时间：2018-03-15 08:29

本文选题：微流控　切入点：载药微球　出处：《中国科学技术大学》2017年硕士论文　论文类型：学位论文

【摘要】：选择合适的载体材料封装药物制成药物缓释系统,能够使药物得到缓释,进而在给病人治疗时可以延长给药间隔,使给药次数大大减少从而减轻病人的痛苦。药物缓释系统有多种制备方法,其中微流控技术可以用来制备微胶囊药物缓释系统。通过改变微流控设备的尺寸和结构以及各相流速的大小可以得到单分散的尺寸结构均一的载药微胶囊。聚二甲基硅氧烷(PDMS)芯片是一种被广泛使用的微流控芯片,然而基于PDMS的结构制作过程较为复杂,通道疏水处理相对复杂并且难以长期循环使用。而基于毛细玻璃管的同轴共射流结构微流控设备制作过程相对简单,成本低,使用同轴共射流微流控设备能制备具有均一大小和结构的微胶囊。封装药物的载体材料有天然高分子材料和人工合成高分子材料,其中乳酸-乙醇酸共聚物(PLGA)是一种常用的合成可降解高分子材料,海藻酸钠是另一种广泛使用的天然可降解药物载体材料。它们都具有无毒,优良的生物相容性,可生物降解性等特点。药物的释放动力学特性深刻的影响着治疗效果,因此近年来多有关于载药微胶囊的药物释放动力学研究。主要体现在对纳米级抗癌药微粒的关注,而对于微米级口服药物缓释微胶囊系统的释放动力学研究分析较为缺少。本文利用毛细玻璃管设计制作微流控设备,以利福平为代表药,分别制备了以PLGA和海藻酸钠为载体的载药微胶囊,并系统的研究了微胶囊大小、形状,释放介质的温度,pH,渗透压,初始药物浓度等因素对体外药物释放动力学的影响。在研究过程中我们发现,微胶囊粒径大小越小,温度越高,药物分子会有更快的初始释放速度和更高的平均释放速度。同时微胶囊的形状结构也会显著影响其释药行为。释放介质渗透压越高,药物释放速度越慢。pH对不同载药基体材料的释放动力学有不同的影响机理。而在一定范围内,初始药物浓度对药物的释放动力学没有明显影响。本文的工作有助于我们了解各因素和药物释放动力学之间的关系,进而可以根据需求设计制备相应的微胶囊使其具有特定的药物释放过程。
[Abstract]:Choosing the right carrier material to encapsulate the drug into a drug delivery system can allow the drug to be released slowly, which in turn can prolong the delivery interval when the patient is treated. Which greatly reduces the pain of the patient. The drug delivery system has a variety of methods of preparation. The microfluidic technology can be used to prepare microcapsule drug delivery system. By changing the size and structure of the microfluidic equipment and the flow rate of each phase, a monodisperse drug loaded microcapsule with uniform size and structure can be obtained. Methylsiloxane PDMS chip is a widely used microfluidic chip. However, the fabrication process of the structure based on PDMS is more complex, the channel hydrophobic treatment is relatively complex and it is difficult to recycle for a long time, while the fabrication process of coaxial cojet structure micro-fluidic device based on capillary glass tube is relatively simple and the cost is low. Microcapsules with uniform size and structure can be prepared by using coaxial cojet microfluidic control equipment. The carrier materials for encapsulating drugs are natural polymer materials and synthetic polymer materials. Among them, lactic acid-glycolic acid copolymer (PLGA) is a commonly used synthetic degradable polymer material, and sodium alginate is another widely used natural biodegradable drug carrier material. The characteristics of biodegradability, such as biodegradability, have a profound impact on the therapeutic effect. Therefore, in recent years, there have been many studies on the pharmacokinetics of microcapsules loaded with drugs, which are mainly reflected in the attention paid to the nanoparticles of anticancer drugs. However, the study on the release kinetics of microscale oral drug sustained-release microcapsule system is scarce. In this paper, a microfluidic device was designed and made with capillary glass tube, and rifampicin was used as the representative drug. Drug loaded microcapsules with PLGA and sodium alginate as carriers were prepared, and the size, shape, temperature and osmotic pressure of the release medium were systematically studied. In the course of the study, we found that the smaller the particle size of microcapsules, the higher the temperature. Drug molecules will have a faster initial release rate and a higher average release rate, and the shape and structure of the microcapsule will significantly affect its release behavior. The higher the osmotic pressure of the release medium, The slower the release rate of the drug is, the more pH has different effects on the release kinetics of different drug-loaded matrix materials, but within a certain range, The initial drug concentration has no obvious effect on the release kinetics of the drug. The work in this paper is helpful to understand the relationship between the various factors and the drug release kinetics. The microcapsules can be designed according to the demand to make them have a specific drug release process.
【学位授予单位】：中国科学技术大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943

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