聚乳酸载柚皮素复合纳米粒的制备、表征及其缓释与抗菌性能

发布时间：2018-04-23 17:21

本文选题：聚乳酸 + 柚皮素　；参考：《太原理工大学》2017年硕士论文

【摘要】：近些年来,以缓控释给药系统、靶向给药系统、经皮给药系统为代表的药物传输系统发展迅猛,为临床治疗提供了更多的选择。其中,缓释和控释系统是发展最快的新型给药系统,具有许多优越性:可缓释药物,从而延长药物作用时间;可在保证疗效的前提下,减少给药剂量,减轻毒副反应;还可提高药物的稳定性。研究者们常将高分子聚合物作为药物载体应用于药物缓释和控释系统,并将它们制备成粒径为1~(-1)000 nm的粒子,这些纳米粒子能穿透组织间隙并被细胞吸收,并通过人体最小的毛细血管。制备聚合物纳米粒的载体材料以合成的可生物降解的聚合物体系和天然的大分子体系为主,其中聚乳酸(PLA)因为良好的生物相容性和生物可降解性被广泛应用。柚皮素是一种具有抗菌、抗氧化、抗溃疡、抑制肝脏的纤维化、抗肿瘤活性的黄酮衍生物。但是,它易氧化,在体内代谢速度快,血药浓度不易控制,存在肝肠循环,口服生物利用度较低,严重制约了其在生物领域的应用。为克服其缺点,本论文采用可降解的聚乳酸为载体,将柚皮素制备成聚乳酸载柚皮素纳米粒,期望能够为今后柚皮素缓释制剂的研究提供一些有价值的参考,促进柚皮素的临床应用。本论文主要工作如下:1、本论文采用改良的溶剂挥发法制备了聚乳酸载柚皮素纳米粒,采用单因素实验分别考察了聚乳酸分子量、聚乳酸质量浓度、油水相体积比、超声时间、投药比以及乳化剂质量分数对纳米粒粒径、载药量和包封率的影响,并筛选出了最佳制备工艺参数;采用场发射扫描电子显微镜、傅立叶红外光谱仪、x射线衍射仪、激光粒度仪、紫外可见分光光度计、酶标仪对纳米粒的形貌、组成、粒径、载药性能、缓释性能和抗菌性能等进行了表征测试。结果表明,最佳制备条件是聚乳酸分子量8万,聚乳酸质量浓度0.03g·ml~(-1),聚乙烯醇(pva)质量分数1%,油水相体积比1:5,超声时间1min,投药比5:1。由最佳工艺制得的载药纳米粒呈圆整球形,平均粒径为135.2nm,分散指数为0.073,载药量为22.3%,包封率为64.7%,且在体外环境下释药时间在250h以上,具有良好的缓释效果。然而其缓释样液在低浓度下(低于20μg·ml~(-1))甚至会促进金黄色葡萄球菌的生长。2、为了提高聚乳酸载柚皮素纳米粒的抗菌性能,本论文将其与淀粉载银纳米颗粒进行复合,制备了聚乳酸包覆柚皮素及淀粉载银复合纳米材料。首先,在本实验室前人工作的基础上,采用液相化学还原法,以葡萄糖为还原剂,淀粉为保护剂制备了淀粉载银纳米颗粒;采用场发射扫描电子显微镜、透射电子显微镜、傅立叶红外光谱仪、x射线衍射仪、激光粒度仪对淀粉载银纳米颗粒的形貌、组成、粒径等进行了表征;然后采用改良的溶剂挥发法制备了聚乳酸复合纳米粒,通过正交实验筛选了最佳的制备工艺条件;采用场发射扫描电子显微镜、透射电子显微镜、X射线衍射仪、激光粒度仪、紫外可见分光光度计、酶标仪对复合纳米粒的形貌、组成、粒径、载药、缓释和抗菌性能等进行了表征测试。结果显示,淀粉载银纳米颗粒呈球形,平均粒径为10.1 nm,分散指数为0.112。制备的聚乳酸复合纳米粒的最佳条件是PLA质量浓度0.03 g·m L~(-1),淀粉载银0.02 g,乳化剂质量分数1%,油水比1:5。该条件下制得的聚乳酸复合纳米粒呈圆整球形,平均粒径为379 nm,分散指数为0.132,载药量为20.8%,包封率为53.8%,其具有良好的抗菌效果,并且柚皮素的缓释效果没有受到影响。
[Abstract]:In recent years, the drug delivery system, targeting drug delivery system, targeted drug delivery system and transdermal drug delivery system, has developed rapidly and provided more options for clinical treatment. The slow release and controlled release system is the fastest developing new drug delivery system, with many advantages: the drug delivery system can be extended to prolong the drug action time; On the premise of ensuring the curative effect, it can reduce the dosage, reduce the side effects, and improve the stability of the drug. The researchers often use polymer as drug carrier in drug release and controlled release system, and prepare particles with a particle size of 1~ (-1) 000 nm, which can penetrate the interstitial space and be absorbed by the cells. A biodegradable polymer system and a natural macromolecular system are synthesized through the preparation of the carrier material of polymer nanoparticles, in which polylactic acid (PLA) is widely used because of its good biocompatibility and biodegradability. Naringenin is an antiseptic, antioxidation, anti ulcer, and inhibiting liver. However, it is easy to oxidize, it is easy to oxidize, it has fast metabolism in the body, the concentration of blood drug is not easy to control, the liver intestine circulation is not easy to be controlled, the oral bioavailability is low, which seriously restricts its application in biological field. In order to overcome its shortcomings, this paper uses degradable polylactic acid as the carrier to prepare naringenin. The lactate naringin nanoparticles are expected to provide some valuable reference for the study of naringin sustained-release preparation in the future. The main work of this thesis is as follows: 1. The paper uses the modified solvent evaporation method to prepare the polylactic naringin nanoparticles, and the single factor experiment is used to investigate the polylactic acid fraction respectively. The effects of the weight, the mass concentration of the polylactic acid, the volume ratio of the oil and water, the time of the ultrasonic, the ratio of the dosage and the mass fraction of the emulsifier on the size of the nanoparticles, the amount of drug loading and the encapsulation efficiency, and the optimum processing parameters were selected. The field emission scanning electron microscope, the Fu Liye infrared spectrometer, the X ray diffractometer, the laser particle size instrument, and the UV visible fraction were used. The morphology, composition, particle size, particle size, drug loading performance, sustained release and antibacterial properties of nanoparticles were characterized by photometer. The results showed that the optimum preparation conditions were 80 thousand of the molecular weight of polylactic acid, 0.03g. Ml~ (-1) of polylactic acid, 1% of polyvinyl alcohol (PVA), 1:5 of oil water phase volume ratio, 1min of ultrasonic time, and dosage of 5:1 The drug loaded nanoparticles obtained by the best process are round and round, with an average particle size of 135.2nm, a dispersion index of 0.073, a drug loading of 22.3%, a encapsulation rate of 64.7%, and a release time of more than 250h in an in vitro environment, with a good release effect. However, the slow-release sample may even promote the golden yellow grape under low concentration (below 20 mu g. Ml~ (-1)). The growth of.2, in order to improve the antibacterial properties of pomelomingin nanoparticles, was combined with starch containing silver nanoparticles to prepare poly (lactic acid) coated naringenin and starch containing silver composite nanomaterials. First, on the basis of previous work in our laboratory, liquid chemical reduction was used as a reducing agent with glucose. Starch loaded silver nanoparticles were prepared as a protector, and the morphology, composition and particle size of the starch loaded silver nanoparticles were characterized by field emission scanning electron microscopy, transmission electron microscopy, Fu Liye infrared spectrometer, X ray diffractometer, and laser particle size analyzer, and then the modified solvent evaporation method was used to prepare the polylactic acid composite. The best preparation conditions were screened by orthogonal experiment. The morphology, composition, particle size, particle size, drug loading, release and antibacterial properties of the composite nanoparticles were characterized by field emission scanning electron microscopy, transmission electron microscopy, X ray diffractometer, laser particle size analyzer, UV visible spectrophotometer and enzyme labeling instrument. The starch carrying silver nanoparticles are spherical, the average particle size is 10.1 nm. The optimum conditions for the poly lactic acid composite nanoparticles prepared by the dispersion index of 0.112. are the PLA mass concentration 0.03 G. M L~ (-1), the starch containing silver 0.02 g, the emulsifier mass fraction 1%, the oil and water ratio of the poly lactic acid composite nanoparticles are round and round, and the average particle size is 37. 9 nm, dispersibility index 0.132, drug loading 20.8%, encapsulation rate 53.8%, it has good antibacterial effect, and naringenin sustained-release effect has not been affected.

【学位授予单位】：太原理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1;TQ460.1

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