本文選題：鹽酸阿霉素 + 脂質(zhì)體�。� 參考：《鄭州大學》2014年碩士論文

【摘要】：鹽酸阿霉素（Doxorubicin，DOX）作為廣譜抗腫瘤藥物，對各種生長周期的腫瘤細胞都有殺滅作用，但較大的心臟毒性限制了其臨床應(yīng)用。單壁碳納米管(Single-walled Carbon Nanotubes，SWNTs)具有獨特的藥物傳遞和光熱治療的性質(zhì)，其巨大的比表面積、大離域π鍵、獨特的跨膜能力及在700～1,100nm范圍的近紅外光下高吸收產(chǎn)熱能力，這些特性使SWNTs可成為一種新型的藥物載體材料。本課題利用脂質(zhì)材料同時包裹SWNTs和阿霉素，構(gòu)建一種腫瘤靶向復合納米給藥體系（Lys/CNTs-DOX-Lip），以期達到化療，光療，熱療三者的協(xié)同作用。 本課題首先利用賴氨酸（Lysine，Lys）對SWNTs進行功能性修飾，然后對Lys/CNTs-DOX-Lip復合制劑的處方和制備工藝進行了研究。通過對實驗影響較大的單因素進行考察，，確定最終處方：磷脂與膽固醇質(zhì)量比為5:1，藥脂比為1:10，探超時間為2min，脂質(zhì)體與碳管比為2:1。最終制備的復合制劑外觀為黑紅色溶液，且放置穩(wěn)定，超濾法測定制劑包封率為85.9%，碳納米管的最終濃度約為200μg·ml-1，阿霉素藥物濃度約為1mg·ml-1。對其藥劑學性質(zhì)研究，測定其粒徑為223±5.9nm，電位為-20±2.3mv。體外釋藥考察了不同的pH環(huán)境條件下對制劑釋藥行為的影響，表明Lys/CNTs-DOX-Lip復合制劑具有明顯的緩釋特性，同時具有一定的pH敏感性。 本課題以SD大鼠為模型動物，采用HPLC法測定血漿中的藥物濃度，研究Lys/CNTs-DOX-Lip復合制劑的體內(nèi)藥代動力學特征。結(jié)果表明：與DOX溶液組相比，Lys/CNTs-DOX-Lip在體內(nèi)具有一定緩釋作用，延長藥物在體內(nèi)的作用時間，提高生物利用度。 本課題以S180荷瘤小鼠為模型動物，采用HPLC測定各組織中的藥物濃度，研究Lys/CNTs-DOX-Lip復合制劑在荷瘤小鼠各組織的分布情況。結(jié)果表明復合制劑具有一定的腫瘤靶向性，減小了心臟毒性。 本課題同時考察了Lys/CNTs-DOX-Lip復合制劑及DOX對照液對S180荷瘤小鼠生命質(zhì)量的影響，以相對腫瘤體積、體重、存活率、飲水量、飲食量等為評價指標；通過在劑量范圍內(nèi)給藥的小鼠的心，肝，脾，肺，腎，腦，瘤等主要組織的HE染色分析，考察給藥系統(tǒng)對小鼠的主要臟器的毒性。結(jié)果表明，Lys/CNTs-DOX-Lip制劑組表現(xiàn)出良好的抗腫瘤效果，且對小鼠的體質(zhì)量，日飲水飲食量未產(chǎn)生影響，精神狀態(tài)良好，生活質(zhì)量得到提高。HE染色結(jié)果表明，Lys/CNTs-DOX-Lip對小鼠的主要臟器在劑量范圍內(nèi)沒有產(chǎn)生明顯的毒性。
[Abstract]:As a broad-spectrum antitumor drug, doxorubicin hydrochloride (Doxorubicindox) can kill tumor cells in various growth cycles, but its clinical application is limited by its large cardiac toxicity. Single-walled Carbon nanotubes (SWNTs) have unique properties of drug delivery and photothermal therapy, their large specific surface area, large delocalized 蟺 bonds, unique transmembrane ability and high absorption of heat under near-infrared light in the range of 700~1100nm. These properties make SWNTs a new drug carrier material. In order to achieve the synergistic effects of chemotherapy, phototherapy and hyperthermia, a tumor targeting compound nano-drug delivery system, Lys-CNTs-DOX-Lipan, was constructed by encapsulating SWNTs and adriamycin with lipids at the same time. In this paper, SWNTs was modified with lysine lys, then the formulation and preparation process of Lys/CNTs-DOX-Lip compound were studied. The results showed that the final prescription was: the mass ratio of phospholipid to cholesterol was 5: 1, the ratio of drug to lipid was 1: 10, the detection time was 2 min, and the ratio of liposome to carbon tube was 2: 1. The final appearance of the composite preparation was black and red solution, and it was stably placed. The entrapment efficiency of the preparation was determined by ultrafiltration method. The final concentration of carbon nanotubes was about 200 渭 g ml-1, and the concentration of adriamycin was about 1mg ml-1. The pharmacological properties were studied. The particle size was 223 鹵5.9 nm and the potential was -20 鹵2.3 MV. The effects of different pH conditions on the drug release behavior were investigated in vitro. The results showed that the Lys/CNTs-DOX-Lip compound had obvious slow-release properties and had certain pH sensitivity. In this study, SD rats were used as model animals to determine the drug concentration in plasma by HPLC method, and to study the pharmacokinetic characteristics of Lys/CNTs-DOX-Lip compound preparation in vivo. The results showed that Lys / CNTs-DOX-Lip had a certain slow-release effect, prolonged the action time and improved the bioavailability compared with the DOX solution group. In this study, S180 tumor bearing mice were used as model animals. The distribution of Lys/CNTs-DOX-Lip compound preparation in tumor bearing mice was studied by HPLC. The results showed that the compound preparation had certain tumor targeting and reduced cardiac toxicity. At the same time, the effects of Lys/CNTs-DOX-Lip compound preparation and DOX control solution on the quality of life of S180 tumor bearing mice were investigated. The relative tumor volume, body weight, survival rate, drinking water, diet and so on were used as evaluation indexes. Liver, spleen, lung, kidney, brain, tumor and other main tissues were analyzed by HE staining to investigate the toxicity of the drug delivery system to the main organs of mice. The results showed that the Lys / CNTs-DOX-Lip preparation group had a good antitumor effect, and had no effect on the body weight and daily drinking diet of mice, and had a good mental state. The results of HE staining showed that Lys / CNTs-DOX-Lip had no obvious toxicity to the main organs of mice in the dose range.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R943

【參考文獻】

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1 ;One patient with metastastic colorectal cancer successfully treated by combination of targeted agents after failure of chemotherpay[J];癌癥;2010年12期

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