本文關(guān)鍵詞： 阿霉素 復(fù)合脂質(zhì)納米圓盤 腫瘤治療 化學治療 藥物緩釋　出處：《哈爾濱工業(yè)大學》2014年碩士論文　論文類型：學位論文

【摘要】：腫瘤分為良性腫瘤和惡性腫瘤兩種，惡性腫瘤又可稱之為癌癥。目前，癌癥已經(jīng)成為了發(fā)達國家人口死亡的最重要原因，并且是發(fā)展中國家人口死亡的第二大原因。隨著我國經(jīng)濟的不斷發(fā)展，近些年我國人民的生活方式也在不斷發(fā)生著改變。一些人在較大的工作壓力下，生活嚴重不規(guī)律，再加上環(huán)境的不斷惡化，導致我國的癌癥患者不斷增加，在癌癥治療方面也面臨著非常嚴峻的形勢。 針對癌癥的傳統(tǒng)化學治療來講，化學藥劑雖然有效，但是其對機體正常細胞的損傷也特別大，甚至有些患者因為經(jīng)受不住化療藥物的副作用而放棄了治療。靶向藥物治療是指開發(fā)出多種納米結(jié)構(gòu)或者常用的基團作為藥物的載體，對化療藥物進行靶向遞送。靶向載體的引入極大改善了傳統(tǒng)化學治療的劣勢，極有可能在不久的將來取代傳統(tǒng)的化學治療方法。但是隨著研究的不斷深入，我們也發(fā)現(xiàn)現(xiàn)有的載體系統(tǒng)自身還有一些問題需要解決：例如，怎樣使藥物定向富集到腫瘤組織處，減少在其他器官的聚集，減小毒副作用；如何增強藥物釋放的可控性和緩釋性，提高藥物的有效性等。所以還需對現(xiàn)有的載體系統(tǒng)進行進一步的完善，或者研制出一種新型的載體系統(tǒng)，克服之前載體系統(tǒng)的缺點，真正做到相容性好、穩(wěn)定性強、毒副作用小和靶向性、緩釋性強。 本課題利用適當比例的長鏈（有機-無機復(fù)合脂質(zhì)）和短鏈脂質(zhì)（DHPC）合成有機-無機復(fù)合脂質(zhì)納米圓盤，該納米圓盤作為一種脂質(zhì)雙層膜結(jié)構(gòu)，是一種很好地生物膜模型，并且表面的硅氧烷網(wǎng)格結(jié)構(gòu)增加了圓盤的穩(wěn)定性，在生物方面具有廣闊的應(yīng)用前景。本課題選取的抗腫瘤藥物為鹽酸阿霉素，，并對鹽酸阿霉素進行處理，合成疏水性阿霉素。鹽酸阿霉素是一種蒽環(huán)類抗癌藥物，可抑制RNA和DNA的合成，對RNA的作用最強，對多種腫瘤均有作用，屬周期非特異性藥物，對各種生長周期的腫瘤細胞都有殺滅作用。但該藥毒性作用較為嚴重，所以有必要開發(fā)新的藥物載體來包裹鹽酸阿霉素，使他的毒副作用減小，穩(wěn)定性增加。本課題利用合成的有機-無機復(fù)合脂質(zhì)納米圓盤包裹疏水性的抗腫瘤藥物阿霉素。對合成載藥粒子進行粒度、紅外、透射電鏡、掃描電鏡表征，證明載藥的復(fù)合脂質(zhì)納米圓盤被成功合成；初步探討納米圓盤對藥物阿霉素的控制釋放性能以及生物相容性。從而為復(fù)合脂質(zhì)納米圓盤應(yīng)用于藥物輸送提供一定的理論基礎(chǔ)。
[Abstract]:Tumors are divided into benign tumors and malignant tumors, which can also be called cancer. At present, cancer has become the most important cause of death in developed countries. It is also the second leading cause of death in developing countries. With the continuous development of our economy, the way of life of our people has been constantly changing in recent years. Some people live under heavy pressure of work, and their lives are very irregular. In addition, the deterioration of the environment leads to an increasing number of cancer patients in China, and also faces a very serious situation in cancer treatment. As for traditional chemotherapy for cancer, although the chemical agent is effective, it also causes great damage to the normal cells of the body. Some patients even give up treatment because they can't stand the side effects of chemotherapy drugs. Targeted drug therapy is the development of a variety of nanostructures or groups commonly used as drug carriers. Targeting delivery of chemotherapeutic drugs. The introduction of targeted vectors has greatly improved the disadvantages of traditional chemotherapy and is likely to replace traditional chemotherapy in the near future. We also found that the existing carrier system itself still has some problems to be solved: for example, how to concentrate the drug into tumor tissue, reduce the accumulation in other organs, and reduce the side effects; How to enhance the controllability and slow-release of drug release, and improve the effectiveness of drugs, etc. Therefore, it is necessary to further improve the existing carrier system, or develop a new carrier system to overcome the shortcomings of the previous carrier system. Good compatibility, strong stability, small toxicity and targeting, strong slow-release. In this paper, the organic-inorganic composite lipid nanodisc was synthesized by using proper proportion of long chain (organic-inorganic compound lipid) and short chain lipid (DHPC). As a kind of lipid bilayer membrane structure, the nano-disk is a very good biofilm model. The siloxane mesh structure on the surface increases the stability of the disc and has a broad prospect in biological application. In this study, adriamycin hydrochloride is selected as the antitumor drug, and doxorubicin hydrochloride is treated with doxorubicin hydrochloride. The synthesis of hydrophobic doxorubicin. Adriamycin hydrochloride is an anthracycline anticancer drug, which can inhibit the synthesis of RNA and DNA, and has the strongest effect on RNA. But the toxicity of the drug is serious, so it is necessary to develop a new drug carrier to encapsulate adriamycin hydrochloride to reduce its side effects. The stability was increased. In this study, the hydrophobic antitumor drug doxorubicin was encapsulated by the synthesized organic-inorganic composite lipid nanodisc. The particle size, infrared, transmission electron microscope and scanning electron microscope of the synthetic drug-loaded particles were characterized. It was proved that the drug loaded composite lipid nanodisc was successfully synthesized, and the controlled release performance and biocompatibility of the nano-disk to drug doxorubicin were discussed, which provided a theoretical basis for the application of the composite lipid nano-disc in drug delivery.
【學位授予單位】：哈爾濱工業(yè)大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R943

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