本文關(guān)鍵詞： 磁-介孔二氧化硅 納米粒子 黃連素 載藥量　出處：《吉林大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：背景： 傳統(tǒng)的細(xì)胞毒抗腫瘤化療藥物，缺少靶向性，治療時(shí)對正常組織器官亦造成損傷，因而限制了其在臨床上的應(yīng)用。近年來，我國采用中醫(yī)中藥對腫瘤進(jìn)行治療已成為腫瘤治療領(lǐng)域的一大特色。黃連素作為一種異喹啉類的生物堿單體化合物，存在于一系列藥用植物中，如黃連、黃柏等，其抗腫瘤效果顯著且毒副作用小。然而，黃連素口服吸收差，生物利用度低等缺點(diǎn)限制了其作為抗腫瘤藥物的臨床應(yīng)用。隨著納米醫(yī)學(xué)的飛速發(fā)展，，納米材料作為藥物載體廣泛的應(yīng)用在腫瘤治療領(lǐng)域，Janus磁-二氧化硅介孔納米粒子（M-MSN）由于其具有優(yōu)良的生物相容性、低毒性、介孔修飾后可控釋藥、磁靶向性等優(yōu)點(diǎn)，適合裝載小分子化療藥物。本研究初次嘗試用Janus磁-介孔二氧化硅納米載體擔(dān)載黃連素，并對增加其載藥率和體外抗腫瘤活性進(jìn)行初步探索。 內(nèi)容： 采用擴(kuò)孔劑均三甲苯（TMB）合成大孔徑磁-介孔二氧化硅，調(diào)整模板劑CTAB在反應(yīng)體系用量改變納米粒子形貌，以及通過增加黃連素在反應(yīng)溶液體系的分散性和溶解度三種方法提高黃連素的載藥量，分別對三種載體的形貌進(jìn)行表征、載藥及釋藥測定，研究空載載體的細(xì)胞安全性和Janus磁-介孔納米藥物載體擔(dān)載黃連素后體外抗腫瘤活性評價(jià)。 結(jié)果： 1.通過TMB構(gòu)建大孔徑的磁-介孔二氧化硅和通過調(diào)整模板劑CTAB用量改變納米粒子的形貌兩種方法，磁-介孔二氧化硅納米粒子形貌發(fā)生改變，但不具有均一性，擔(dān)載黃連素的載藥量沒有明顯提高。采用DMSO作為溶劑改變黃連素的溶解度和分散性的方法合成的Janus磁-介孔二氧化硅形貌均一，擔(dān)載黃連素的載藥率和載藥量有明顯提高。 2.采用DMSO作為溶劑增加黃連素的溶解度和分散性的方法所合成的Janus磁-介孔二氧化硅黃連素納米載體系統(tǒng)，黃連素的載藥率約為47%，載藥量為20%�？蛰d載體細(xì)胞安全性良好，50μg/ml濃度以下基本無毒。Janus磁-介孔二氧化硅納米載體擔(dān)載黃連素后對肝癌細(xì)胞HepG2的細(xì)胞毒性隨著載藥系統(tǒng)的濃度增加而增大，12.5～50μg/ml載體系統(tǒng)（擔(dān)載黃連素2.5-10μg/ml）與HepG2共孵育48h,其細(xì)胞殺傷作用強(qiáng)于等濃度黃連素組。 結(jié)論： 利用TMB擴(kuò)孔的方法，以及調(diào)整CTAB在反應(yīng)體系中用量兩種方法均無法提高黃連素的載藥量，而通過增加黃連素在反應(yīng)體系中溶解度的方法合成的Janus磁-介孔二氧化硅黃連素納米載體系統(tǒng)，提高了黃連素的載藥率和載藥量。Janus磁-介孔二氧化硅納米空載體在50μg/ml濃度以下體外基本無毒。Janus磁-介孔二氧化硅擔(dān)載黃連素的納米載藥系統(tǒng)對腫瘤細(xì)胞殺傷具有劑量依賴性，12.5～50μg/ml載體系統(tǒng)（擔(dān)載黃連素2.5～10μg/ml）細(xì)胞殺傷作用強(qiáng)于等濃度黃連素組。
[Abstract]:Background:. The traditional cytotoxic anti-tumor chemotherapeutic drugs lack of targeting and damage to normal tissues and organs during treatment, which limits their clinical application in recent years. Chinese traditional medicine has become a major feature in the field of tumor treatment. Berberine, as an isoquinoline alkaloid monomer, exists in a series of medicinal plants, such as Coptis chinensis, Cortex Phellodendri, etc. However, the poor absorption of berberine and its low bioavailability limit its clinical application as an antitumor drug. Nanomaterials are widely used as drug carriers in the field of tumor therapy because of their excellent biocompatibility, low toxicity, controlled release after mesoporous modification and magnetic targeting. It is suitable for loading small molecular chemotherapeutic drugs. In this study, Janus magnetic-mesoporous silica nano-carrier was used to support berberine for the first time, and to increase the drug loading rate and anti-tumor activity in vitro. Content:. The large aperture magnetic-mesoporous silica was synthesized by using the pore expander (TMB), and the dosage of template agent CTAB was adjusted to change the morphology of nanoparticles in the reaction system. By increasing the dispersity and solubility of berberine in the reaction solution, the drug loading of berberine was increased, and the morphology of the three carriers was characterized, and the drug loading and drug release were determined. To study the cell safety of no-load carrier and the evaluation of anti-tumor activity of Janus magnetic-mesoporous drug carrier loaded with berberine in vitro. Results:. 1. The morphology of magneto-mesoporous silica with large pore size was changed by TMB and the morphology of nano-particles was changed by adjusting the amount of template CTAB. The amount of berberine loaded was not significantly increased. The morphology of Janus synthesized by using DMSO as solvent to change the solubility and dispersion of berberine was uniform, and the drug loading rate and amount of loaded berberine were improved obviously. 2. The Janus magnetic-mesoporous silica nano-carrier system was synthesized by using DMSO as solvent to increase the solubility and dispersion of berberine. The drug loading rate of berberine is about 47 and the drug load is 20. The safety of the empty carrier cells is good. The cytotoxicity of berberine loaded on the HepG2 cell line of hepatoma cells after carrying berberine on the magnetic mesoporous silica nano-carrier is basically nontoxic under the concentration of 50 渭 g / ml. When the concentration of berberine was increased, and the 50 渭 g / ml carrier system (supported berberine 2.5-10 渭 g / ml) was incubated with HepG2 for 48 h, the cytotoxicity of the cells was stronger than that of the same concentration of berberine group. Conclusion:. The methods of TMB reaming and adjusting the dosage of CTAB in the reaction system could not increase the amount of berberine loaded. The Janus magnetic-mesoporous silica nano-carrier system was synthesized by increasing the solubility of berberine in the reaction system. The drug loading rate and drug load of berberine. Janus magnetic-mesoporous silica nano-space carrier is basically nontoxic in vitro under 50 渭 g / ml. Janus magnetic-mesoporous silica loaded berberine system can kill tumor cells. The cytotoxicity of the 50 渭 g / ml carrier system (supported berberine 2.510 渭 g / ml) was stronger than that of the same concentration of berberine.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：TB383.1;TQ127.2

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