磁性药物靶向递送中药物捕获效率建模及影响因素分析

发布时间：2018-07-29 14:54

【摘要】：视网膜血管阻塞性疾病是一种严重损害视功能的常见病。传统常规治疗如按摩、穿刺、口服药物等方式,需要较长的时间,且治愈效果不明显。磁性药物靶向递送是将药物装载到磁性纳米颗粒上,借助于外部磁场,将载体定向于靶区,使其所含药物定位释放集中在病变部位发挥作用,具有高靶向性、速效和低毒的特点。将磁性药物靶向方法应用于视网膜血管阻塞性疾病的治疗具有特别的临床意义。目前,国内对于磁性药物靶向治疗的整体发展水平仍处于基础研究阶段,还存在许多不足,且缺少视网膜血管中栓塞对磁性药物捕获效率等方面的研究。为此,论文结合上海交通大学医理工基金项目《经眼动脉介入释放纳米材料携载t-PA靶向治疗视网膜静脉阻塞的实验研究》,从理论、试验两方面着重对磁性药物靶向传递中药物捕获效率计算模型及影响因素等进行细致的研究。本文主要完成的工作及取得成果如下: 1、根据视网膜血管的特点以及细小血管内血液的非牛顿流体流动状态,选择了卡森模型表示内层血液特性,选择牛顿模型表示外层血浆特性。区别于以往研究采用无限长永磁铁,本文采用矩形永磁铁,作为外部磁场源,基于两相卡森-牛顿模型,分析了携带药物的磁性纳米颗粒在血管中受磁力和流体力作用的运动轨迹,建立了磁颗粒三维空间的捕获效率的理论公式,此模型比传统模型更精确;进而获得磁性药物捕获体积的优化模型。 2、采用龙格库塔算法和二分法,通过Matlab数值仿真,分析了血管内流场和磁场分布,得到了不同模型血液流速、磁颗粒运动轨迹、捕获效率,并比较了平面和三维捕获效率。仿真结果表明,使用非牛顿卡森流体可以更好描述血液,矩形永磁铁产生的磁场更有效;其他条件不变时,颗粒半径越大、磁性物质半径比越大、磁场强度越大、磁铁与血管距离越小、血管半径越小,捕获效率越大;不同颗粒半径时的,磁性物质半径比为0.75时捕获的药物捕获体积最大,在磁性药物制备过程中,可以参考这个值,达到系统优化。 3、基于视网膜眼底血管栓塞的成因和临床表现,针对不同情况,本文建立了刚性和弹性栓塞血管模型,并借助Gambit和Fluent进行了模型的CFD仿真,从理论上分析了血管栓塞对血液流速、压力等的影响,以及在磁性药物靶向系统中,栓塞大小、血管弹性、磁场范围等对磁颗粒捕获效率的影响,为临床治疗提供了理论依据。 4、通过体外实验分析了溶液流速和磁场强度对磁颗粒捕获效率的影响,验证了本文建立的磁颗粒捕获模型的有效性,且它比传统模型精确稳定。同时实验过程中碰到的问题及解决方法,如磁颗粒捕获平衡等,对后续实验乃至人体实验提供了参考。综上所述,将磁性药物靶向方法应用于视网膜血管阻塞性疾病的治疗,可提高药物的药效,具有广泛的用途和潜在的巨大市场需求。本文研究工作及成果为磁性药物靶向方法运用于视网膜血管阻塞疾病的治疗提供了理论指导。
[Abstract]:Retinal vascular obstruction is a common disease which seriously damages the visual function. Traditional conventional treatment, such as massage, puncture and oral medicine, takes a long time, and the effect is not obvious. The target delivery of magnetic drugs is to load the drug onto magnetic nanoparticles, and the carrier is directed to the target area with the help of the external magnetic field. The drug targeting release concentrates on the site of the lesion, which has the characteristics of high targeting, rapid and low toxicity. The application of magnetic drug targeting to the treatment of retinal vascular obstruction is of special clinical significance. At present, the overall development level of magnetic drug targeting therapy is still in the basic research stage at home. There are still many shortcomings and lack of research on magnetic drug capture efficiency in retinal vascular embolization. To this end, the thesis combines the medical science and Technology Fund Project of Shanghai Jiao Tong University with the experimental research on the treatment of retinal vein occlusion with t-PA targeted by the interventional release nanomaterials of the ophthalmic artery, which focuses on the two aspects of the theory and experiment. The drug capture efficiency calculation model and influencing factors in object oriented transfer were studied in detail.
The main work and achievements in this paper are as follows:
1, according to the characteristics of retinal blood vessels and the flow state of the non Newton fluid in the blood in the small blood vessels, the Carson model is selected to represent the inner blood characteristics and the Newton model is selected to represent the outer plasma characteristics. The model is used to analyze the trajectory of magnetic nanoparticles carrying magnetic and fluid forces in the blood vessels. The theoretical formula of the capture efficiency of the magnetic particle three-dimensional space is established. This model is more accurate than the traditional model, and then the optimization model of the magnetic drug capture volume is obtained.
2, using the Runge Kutta algorithm and the dichotomy, the flow field and magnetic field distribution in the blood vessel are analyzed by Matlab numerical simulation. The blood flow velocity, the magnetic particle trajectory, the capture efficiency and the capture efficiency are obtained. The simulation results show that the use of non Newtonian Carson fluid can better describe the blood, rectangular permanent magnet. The magnetic field is more effective. When the other conditions are constant, the larger the particle radius, the larger the magnetic material radius, the greater the magnetic field, the smaller the distance between the magnet and the blood vessel, the smaller the radius of the blood vessel, the greater the capture efficiency, and the largest capture volume of the magnetic material when the radius of magnetic material is 0.75, and in the preparation of magnetic drugs. You can refer to this value to achieve system optimization.
3, based on the causes and clinical manifestations of retinal vascular embolization, a rigid and elastic embolic vascular model was established in this paper, and the CFD simulation of the model was carried out with Gambit and Fluent. The effect of vascular embolization on blood flow velocity, pressure and so on, and the size of embolization in magnetic drug targeting system were analyzed theoretically. The effect of vascular elasticity and magnetic field on the efficiency of magnetic particle capture provides a theoretical basis for clinical treatment.
4, the effect of the solution velocity and magnetic field intensity on the magnetic particle capture efficiency is analyzed in vitro, and the validity of the magnetic particle capture model is verified, and it is more accurate than the traditional model. At the same time, the problems encountered in the process and the solution, such as the balance of magnetic particle capture, are proposed to the follow-up experiment and the human experiment. For reference.
In summary, the application of the magnetic drug targeting method to the treatment of retinal vascular obstruction can improve the efficacy of the drug, and have extensive use and potential huge market demand. The work and results of this paper provide theoretical guidance for the application of magnetic drug targeting to the treatment of retinal vascular obstruction disease.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：TH786;R94

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