功能聚合物纳米粒的合成及其药物释放性能研究

发布时间：2018-08-03 19:58

【摘要】：功能高分子医用材料在生物药剂的发展应用中发挥着十分重要的作用。功能高分子材料的应用可以有效改善生物药剂的安全性,合理性,精密性,以便更好的实现预期的疗效。聚合物纳米粒是高分子材料在生物医药领域的应用,其在降低小分子药物的毒害作用,实现亲疏水药物在体内循环的控释,及其在药物靶向传递中具有明显的优势。建立多功能药物释放体系的释放机制依赖于具有不同功能的聚合物材料[1]。本文旨在研究多功能聚合物纳米粒的设计、合成及其药物释放性能。采用天然高分子材料壳聚糖(CS)、温敏材料聚N-异丙基丙烯酰胺(PNIPAM)及一些单体,合成了一系列具有不同功能的聚合物纳米粒子。最后围绕纳米粒的药物负载能力及不同条件下纳米粒的药物释放行为展开研究,具体研究内容如下:(1)通过接枝共聚法,利用不同单体,如甲基丙烯酸甲酯(MMA)、丙烯酸(AA)和N-异丙基丙烯酰胺(NIPAM)等对CS进行接枝改性,合成了一系列壳聚糖基纳米水凝胶(CS-based NHs)材料。对比了不同NHs材料对抗癌药物5-氟尿嘧啶(5-FU)的负载能力及5-FU在不同环境下的释放性能。研究表明:制备的NHs为粒径分布在140-190 nm的均一球型,携带正电荷,组分不同的NHs展示了不同的pH稳定性。NHs对5-FU的最大负载率可达99.5%。5-FU-loaded NHs在模拟体液(pH 7.4)、胃液(pH 1.2)和肠液(p H 6.8)环境下,NHs均能实现5-FU的连续释放。(2)通过自由基聚合,合成了两亲性嵌段共聚物聚(N-异丙基丙烯酰胺-co-丙烯酸)(P(NIPAM-co-AA))。通过对P(NIPAM-co-AA)接枝半胱氨酸(Cys),又制备了P(NIPAM-co-AA)-g-Cys。利用超声波辐射技术,两亲性共聚物将含有疏水性药物的羟基硅油包覆,并在油水界面交联成膜,形成水包油的微胶囊(MCs)结构,实现了共聚物作为疏水性药物载体的功能。为了得到良好的聚合物微胶囊(polymer-based MCs),主要考察了超声模式、超声功率、超声时间、聚合物的浓度、水油比等一系列条件对MCs形貌与性质的影响。最终确定了最佳的实验条件为脉冲超声输出模式,超声功率为250 W,共聚物浓度为1 wt.%,水油比为5:1,得到的产物粒径均一,其平均粒径约为1.0μm。其次,探究了polymer-based MCs在不同环境下药物控制释放的智能响应性。研究表明:MCs具有良好的药物负载能力和稳定性。通过不同条件下MCs的药物释放实验,证明了C6-loaded P(NIPAM-co-AA)MCs具有温度和pH双重响应性,C6-loaded P(NIPAM-co-AA)-g-Cys MCs具有温度和还原双重响应性,并且两种polymer-based MCs均展现了良好的药物释放性能。
[Abstract]:Functional polymer medical materials play an important role in the development and application of biological agents. The application of functional polymer materials can effectively improve the safety, rationality and precision of biological agents. Polymer nanoparticles are the applications of polymer materials in the field of biomedicine. They have obvious advantages in reducing the toxicity of small molecular drugs, realizing the controlled release of hydrophilic drugs in vivo, and in the targeted delivery of drugs. The release mechanism of multifunctional drug release system depends on polymer materials with different functions [1]. The purpose of this paper is to study the design, synthesis and drug release properties of multifunctional polymer nanoparticles. A series of polymer nanoparticles with different functions were synthesized by using natural polymer chitosan (CS), thermosensitive material poly (N-isopropylacrylamide) (PNIPAM) and some monomers. Finally, the drug loading capacity of nanoparticles and the drug release behavior of nanoparticles under different conditions are studied. The specific contents are as follows: (1) by graft copolymerization, different monomers are used. A series of chitosan based nano-hydrogels (CS-based NHs) were synthesized by grafting CS with methyl methacrylate (MMA), acrylic acid (AA) and N-isopropyl acrylamide (NIPAM). The loading capacity of different NHs materials on the anticancer drug 5 fluorouracil (5-FU) and the release performance of 5-FU in different environments were compared. The results show that the prepared NHs is a homogeneous sphere with a particle size distribution of 140-190 nm and carries a positive charge. NHs with different components showed that the maximum loading rate of 5-FU under different pH stability. NHs could reach to 99.5%.5-FU-loaded NHs in simulated body fluid (pH 7.4), gastric juice (pH 1.2) and intestinal fluid (p H 6.8). (2) continuous release of 5-FU was achieved by free radical polymerization. The amphiphilic block copolymer (N- isopropylacrylamide-co- acrylic acid) (P (NIPAM-co-AA).) was synthesized. P (NIPAM-co-AA) -g-Cys was prepared by grafting P (NIPAM-co-AA) with cysteine (Cys),. The hydroxy silicone oil containing hydrophobic drugs was coated with amphiphilic copolymers by ultrasonic radiation and cross-linked at the oil-water interface to form a microencapsulated (MCs) structure of water-in-oil. The function of the copolymers as a hydrophobic drug carrier was realized. In order to obtain good polymer microcapsules (polymer-based MCs), the effects of ultrasonic mode, ultrasonic power, ultrasonic time, polymer concentration and water-oil ratio on the morphology and properties of MCs were investigated. The optimal experimental conditions were determined as follows: the ultrasonic power was 250W, the copolymer concentration was 1wt.and the water-oil ratio was 5: 1. The average particle size of the product was about 1.0 渭 m. Secondly, the intelligent response of polymer-based MCs to controlled drug release in different environments was investigated. The results showed that MCs had good drug loading ability and stability. Through the drug release experiments of MCs under different conditions, it was proved that C6-loaded P (NIPAM-co-AA) MCs had dual temperature and pH responses to C6-loaded P (NIPAM-co-AA) -g-Cys MCs, and both polymer-based MCs showed good drug release performance.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：TQ460.1;O631.3

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