本文選題：藥物靶向遞送　切入點(diǎn)：磁性載藥微粒　出處：《重慶大學(xué)》2014年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：傳統(tǒng)的藥物傳遞系統(tǒng)通常采取靜脈注射的方式將藥物運(yùn)送到血管中，然后通過(guò)血液自身的流動(dòng)將注射的藥物帶動(dòng)到全身以及病變的區(qū)域，由于藥物分散到全身，在病變區(qū)域的相對(duì)濃度較低，所能達(dá)到的治療效果相對(duì)較低，可能導(dǎo)致治療周期性延長(zhǎng)，治愈效果減弱。如欲獲得更理想的治療效果，就必須加大藥物劑量，這樣就能在目標(biāo)區(qū)域得到治療的理想濃度，但是藥物對(duì)正常細(xì)胞會(huì)產(chǎn)生負(fù)面效果，對(duì)人體帶來(lái)一定程度的損傷。為了克服傳統(tǒng)醫(yī)學(xué)上的這些問(wèn)題，人們提出了許多藥物靶向遞送的方法，但是這些方法都還處于理論和模擬階段，應(yīng)用到臨床中尚需時(shí)日。其中的一種方法，即將治療藥物包裹到磁性納米顆粒上，然后通過(guò)外部條件的控制有效地實(shí)現(xiàn)顆粒在體內(nèi)有目的的傳送、聚集和對(duì)已經(jīng)病變的區(qū)域?qū)崿F(xiàn)靶向性的治療。實(shí)用上，可將治療藥物裹覆在集群磁性顆粒的表面，通過(guò)外部放置磁場(chǎng)的定向引導(dǎo),最終將藥物遞送到體內(nèi)發(fā)生病變的區(qū)域目的性的釋放。如此不僅降低了傳統(tǒng)遞送的缺點(diǎn)以及毒副作用,而且更直接地增加了局部區(qū)域的藥物濃度,有利于提高治療，降低藥物對(duì)正常細(xì)胞的副作用。這些藥物靶向輸運(yùn)的優(yōu)越性無(wú)疑對(duì)包括癌癥在內(nèi)的疾病的治療具有巨大的應(yīng)用前景和市場(chǎng)需求。 本文介紹了在血液的粘性和外磁場(chǎng)作用下載藥物微粒在血管中的流動(dòng)、聚集等力學(xué)特性，建立了一個(gè)數(shù)學(xué)模型。進(jìn)而忽略顆粒的重力、浮力等影響以及顆粒之間的相互作用，重點(diǎn)分析了粘性阻力和磁場(chǎng)力對(duì)顆粒流動(dòng)的作用，提出了載體顆粒的流動(dòng)模型。模型從理論上描述了磁性載體顆粒在血管中流動(dòng)時(shí)磁矩對(duì)顆粒軌跡的影響以及微粒半徑對(duì)顆粒捕捉效率以及與磁場(chǎng)強(qiáng)度的關(guān)系。借助Matlab數(shù)值分析了磁性載體微粒的運(yùn)動(dòng)過(guò)程;用計(jì)算流體力學(xué)方法和Fluent軟件模擬了磁矩、顆粒半徑等對(duì)磁顆粒捕獲的作用;仿真結(jié)果與數(shù)值結(jié)果基本一致,得到了三維空間中不同條件的捕獲效率。 由于外部磁場(chǎng)條件的導(dǎo)向，，取得了治療藥物目的性聚集的效果。數(shù)學(xué)模型模擬結(jié)果和仿真結(jié)果有相似的顆粒聚集特征。因此，本文中提出的數(shù)學(xué)模型在一定條件下描述了載藥顆粒的流動(dòng)、聚集與外部磁場(chǎng)強(qiáng)度的關(guān)系。利用所提出的流體動(dòng)模型分析了磁性載體的流動(dòng)與顆粒半徑和磁矩的關(guān)系，可為磁性藥物靶向遞送的應(yīng)用提供參考。
[Abstract]:The traditional drug delivery system usually carries drugs into the blood vessels by intravenous injection, and then drives the injected drugs to the whole body and the diseased areas through the flow of the blood itself, because the drugs are dispersed throughout the body. The relative concentration in the diseased area is relatively low and the therapeutic effect is relatively low, which may lead to the prolongation of the treatment cycle and the weakening of the cure effect. If you want to obtain a better therapeutic effect, you must increase the dosage of the drug. In this way, the ideal concentration of treatment can be obtained in the target area, but the drug will have a negative effect on normal cells and cause a certain degree of damage to the human body. In order to overcome these problems in traditional medicine, Many methods of targeted delivery of drugs have been proposed, but these methods are still in the theoretical and simulation stages and will take some time to be applied to clinical applications. One of them is that therapeutic drugs are encapsulated on magnetic nanoparticles. Then through the control of external conditions, the particles can be effectively transported, aggregated and targeted treatment of the diseased areas in vivo. In practice, the therapeutic drugs can be coated on the surface of the cluster magnetic particles. Through the directional guidance of the external magnetic field, the drug is eventually delivered to the disease-causing region of the body for purposeful release, which not only reduces the disadvantages of traditional delivery, but also reduces the side effects. And more directly increases the concentration of drugs in local areas, which is helpful to improve the treatment. The advantages of targeted delivery of these drugs undoubtedly have great application prospects and market demand for the treatment of diseases including cancer. In this paper, the flow and aggregation of drug particles in blood vessels are introduced, and a mathematical model is established. The effects of gravity and buoyancy of particles and the interaction between particles are ignored. The effects of viscous resistance and magnetic field force on particle flow are emphatically analyzed. A flow model of carrier particles is proposed, which theoretically describes the effect of magnetic moment on particle trajectory and the relationship between particle radius and particle capture efficiency and magnetic field intensity. The moving process of magnetic carrier particles is analyzed numerically by Matlab. The effect of magnetic moment and particle radius on magnetic particle capture is simulated by using computational fluid dynamics method and Fluent software. The simulation results are in good agreement with the numerical results, and the capture efficiency of different conditions in three-dimensional space is obtained. Due to the guidance of external magnetic field conditions, the therapeutic effect of targeted drug aggregation is achieved. The simulation results of the mathematical model and the simulation results have similar particle aggregation characteristics. The mathematical model proposed in this paper describes the relationship between the flow, aggregation and external magnetic field intensity of the drug-loaded particles under certain conditions. The relationship between the flow of the magnetic carrier and the particle radius and magnetic moment is analyzed by using the proposed fluid dynamic model. It can provide reference for the application of magnetic drug targeted delivery.
【學(xué)位授予單位】：重慶大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R943

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