磁性藥物靶向遞送中藥物捕獲效率建模及影響因素分析
發(fā)布時間：2018-07-29 14:54
【摘要】：視網(wǎng)膜血管阻塞性疾病是一種嚴(yán)重?fù)p害視功能的常見病。傳統(tǒng)常規(guī)治療如按摩、穿刺、口服藥物等方式,需要較長的時間,且治愈效果不明顯。磁性藥物靶向遞送是將藥物裝載到磁性納米顆粒上,借助于外部磁場,將載體定向于靶區(qū),使其所含藥物定位釋放集中在病變部位發(fā)揮作用,具有高靶向性、速效和低毒的特點。將磁性藥物靶向方法應(yīng)用于視網(wǎng)膜血管阻塞性疾病的治療具有特別的臨床意義。目前,國內(nèi)對于磁性藥物靶向治療的整體發(fā)展水平仍處于基礎(chǔ)研究階段,還存在許多不足,且缺少視網(wǎng)膜血管中栓塞對磁性藥物捕獲效率等方面的研究。為此,論文結(jié)合上海交通大學(xué)醫(yī)理工基金項目《經(jīng)眼動脈介入釋放納米材料攜載t-PA靶向治療視網(wǎng)膜靜脈阻塞的實驗研究》,從理論、試驗兩方面著重對磁性藥物靶向傳遞中藥物捕獲效率計算模型及影響因素等進(jìn)行細(xì)致的研究。 本文主要完成的工作及取得成果如下: 1、根據(jù)視網(wǎng)膜血管的特點以及細(xì)小血管內(nèi)血液的非牛頓流體流動狀態(tài),選擇了卡森模型表示內(nèi)層血液特性,選擇牛頓模型表示外層血漿特性。區(qū)別于以往研究采用無限長永磁鐵,本文采用矩形永磁鐵,作為外部磁場源,基于兩相卡森-牛頓模型,分析了攜帶藥物的磁性納米顆粒在血管中受磁力和流體力作用的運動軌跡,建立了磁顆粒三維空間的捕獲效率的理論公式,此模型比傳統(tǒng)模型更精確;進(jìn)而獲得磁性藥物捕獲體積的優(yōu)化模型。 2、采用龍格庫塔算法和二分法,通過Matlab數(shù)值仿真,分析了血管內(nèi)流場和磁場分布,得到了不同模型血液流速、磁顆粒運動軌跡、捕獲效率,并比較了平面和三維捕獲效率。仿真結(jié)果表明,使用非牛頓卡森流體可以更好描述血液,矩形永磁鐵產(chǎn)生的磁場更有效;其他條件不變時,顆粒半徑越大、磁性物質(zhì)半徑比越大、磁場強(qiáng)度越大、磁鐵與血管距離越小、血管半徑越小,捕獲效率越大;不同顆粒半徑時的,磁性物質(zhì)半徑比為0.75時捕獲的藥物捕獲體積最大,在磁性藥物制備過程中,可以參考這個值,達(dá)到系統(tǒng)優(yōu)化。 3、基于視網(wǎng)膜眼底血管栓塞的成因和臨床表現(xiàn),針對不同情況,本文建立了剛性和彈性栓塞血管模型,并借助Gambit和Fluent進(jìn)行了模型的CFD仿真,從理論上分析了血管栓塞對血液流速、壓力等的影響,以及在磁性藥物靶向系統(tǒng)中,栓塞大小、血管彈性、磁場范圍等對磁顆粒捕獲效率的影響,為臨床治療提供了理論依據(jù)。 4、通過體外實驗分析了溶液流速和磁場強(qiáng)度對磁顆粒捕獲效率的影響,驗證了本文建立的磁顆粒捕獲模型的有效性,且它比傳統(tǒng)模型精確穩(wěn)定。同時實驗過程中碰到的問題及解決方法,如磁顆粒捕獲平衡等,對后續(xù)實驗?zāi)酥寥梭w實驗提供了參考。 綜上所述,將磁性藥物靶向方法應(yīng)用于視網(wǎng)膜血管阻塞性疾病的治療,可提高藥物的藥效,具有廣泛的用途和潛在的巨大市場需求。本文研究工作及成果為磁性藥物靶向方法運用于視網(wǎng)膜血管阻塞疾病的治療提供了理論指導(dǎo)。
[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.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：TH786;R94
本文編號：2153036
[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.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：TH786;R94
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