本文選題：微流控　切入點：載藥微球　出處：《中國科學(xué)技術(shù)大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：選擇合適的載體材料封裝藥物制成藥物緩釋系統(tǒng),能夠使藥物得到緩釋,進而在給病人治療時可以延長給藥間隔,使給藥次數(shù)大大減少從而減輕病人的痛苦。藥物緩釋系統(tǒng)有多種制備方法,其中微流控技術(shù)可以用來制備微膠囊藥物緩釋系統(tǒng)。通過改變微流控設(shè)備的尺寸和結(jié)構(gòu)以及各相流速的大小可以得到單分散的尺寸結(jié)構(gòu)均一的載藥微膠囊。聚二甲基硅氧烷(PDMS)芯片是一種被廣泛使用的微流控芯片,然而基于PDMS的結(jié)構(gòu)制作過程較為復(fù)雜,通道疏水處理相對復(fù)雜并且難以長期循環(huán)使用。而基于毛細玻璃管的同軸共射流結(jié)構(gòu)微流控設(shè)備制作過程相對簡單,成本低,使用同軸共射流微流控設(shè)備能制備具有均一大小和結(jié)構(gòu)的微膠囊。封裝藥物的載體材料有天然高分子材料和人工合成高分子材料,其中乳酸-乙醇酸共聚物(PLGA)是一種常用的合成可降解高分子材料,海藻酸鈉是另一種廣泛使用的天然可降解藥物載體材料。它們都具有無毒,優(yōu)良的生物相容性,可生物降解性等特點。藥物的釋放動力學(xué)特性深刻的影響著治療效果,因此近年來多有關(guān)于載藥微膠囊的藥物釋放動力學(xué)研究。主要體現(xiàn)在對納米級抗癌藥微粒的關(guān)注,而對于微米級口服藥物緩釋微膠囊系統(tǒng)的釋放動力學(xué)研究分析較為缺少。本文利用毛細玻璃管設(shè)計制作微流控設(shè)備,以利福平為代表藥,分別制備了以PLGA和海藻酸鈉為載體的載藥微膠囊,并系統(tǒng)的研究了微膠囊大小、形狀,釋放介質(zhì)的溫度,pH,滲透壓,初始藥物濃度等因素對體外藥物釋放動力學(xué)的影響。在研究過程中我們發(fā)現(xiàn),微膠囊粒徑大小越小,溫度越高,藥物分子會有更快的初始釋放速度和更高的平均釋放速度。同時微膠囊的形狀結(jié)構(gòu)也會顯著影響其釋藥行為。釋放介質(zhì)滲透壓越高,藥物釋放速度越慢。pH對不同載藥基體材料的釋放動力學(xué)有不同的影響機理。而在一定范圍內(nèi),初始藥物濃度對藥物的釋放動力學(xué)沒有明顯影響。本文的工作有助于我們了解各因素和藥物釋放動力學(xué)之間的關(guān)系,進而可以根據(jù)需求設(shè)計制備相應(yīng)的微膠囊使其具有特定的藥物釋放過程。
[Abstract]:Choosing the right carrier material to encapsulate the drug into a drug delivery system can allow the drug to be released slowly, which in turn can prolong the delivery interval when the patient is treated. Which greatly reduces the pain of the patient. The drug delivery system has a variety of methods of preparation. The microfluidic technology can be used to prepare microcapsule drug delivery system. By changing the size and structure of the microfluidic equipment and the flow rate of each phase, a monodisperse drug loaded microcapsule with uniform size and structure can be obtained. Methylsiloxane PDMS chip is a widely used microfluidic chip. However, the fabrication process of the structure based on PDMS is more complex, the channel hydrophobic treatment is relatively complex and it is difficult to recycle for a long time, while the fabrication process of coaxial cojet structure micro-fluidic device based on capillary glass tube is relatively simple and the cost is low. Microcapsules with uniform size and structure can be prepared by using coaxial cojet microfluidic control equipment. The carrier materials for encapsulating drugs are natural polymer materials and synthetic polymer materials. Among them, lactic acid-glycolic acid copolymer (PLGA) is a commonly used synthetic degradable polymer material, and sodium alginate is another widely used natural biodegradable drug carrier material. The characteristics of biodegradability, such as biodegradability, have a profound impact on the therapeutic effect. Therefore, in recent years, there have been many studies on the pharmacokinetics of microcapsules loaded with drugs, which are mainly reflected in the attention paid to the nanoparticles of anticancer drugs. However, the study on the release kinetics of microscale oral drug sustained-release microcapsule system is scarce. In this paper, a microfluidic device was designed and made with capillary glass tube, and rifampicin was used as the representative drug. Drug loaded microcapsules with PLGA and sodium alginate as carriers were prepared, and the size, shape, temperature and osmotic pressure of the release medium were systematically studied. In the course of the study, we found that the smaller the particle size of microcapsules, the higher the temperature. Drug molecules will have a faster initial release rate and a higher average release rate, and the shape and structure of the microcapsule will significantly affect its release behavior. The higher the osmotic pressure of the release medium, The slower the release rate of the drug is, the more pH has different effects on the release kinetics of different drug-loaded matrix materials, but within a certain range, The initial drug concentration has no obvious effect on the release kinetics of the drug. The work in this paper is helpful to understand the relationship between the various factors and the drug release kinetics. The microcapsules can be designed according to the demand to make them have a specific drug release process.
【學(xué)位授予單位】：中國科學(xué)技術(shù)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R943

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