發(fā)布時間：2018-10-14 16:22

【摘要】：近年來智能響應(yīng)型納米藥物在藥物釋放控制體系中受到廣泛關(guān)注。它對于控制藥物釋放速度、減小藥物的副作用等有重要意義。而針對人體不同組織結(jié)構(gòu)微環(huán)境的pH微小變化(正常組織細(xì)胞的pH值接近中性,而病變組織細(xì)胞的pH值在5.5-6.9之間),pH響應(yīng)的智能靶向藥物逐步成為關(guān)注的熱點(diǎn)。本文制備出一種分散性好、體外細(xì)胞毒性低的pH敏感型磁靶向納米載體,并對它的載藥性能進(jìn)行了研究。主要工作如下：1.采用發(fā)散法制備了0.5G到2.5G的聚酰胺-胺(PAMAM)樹枝狀大分子,并根據(jù)產(chǎn)品的產(chǎn)率和純度分析出PAMAM合成的最佳條件為：最佳溫度25℃,最佳反應(yīng)時間24h,最佳的投料比例為mol上一代PAMAM:molEDA/MA=1:24。2.分別采用水熱法和化學(xué)共沉淀法制備出分散性良好的磁性Fe304納米粒子,并對其表面進(jìn)行改性,制備出親水的氨基化Fe3O4。表征結(jié)果表明：經(jīng)過APTES改性后得到的氨基化Fe304為分散性較好的球形粒子,粒徑約17nm,磁含量為81%,具有良好的磁響應(yīng)性能。3.實(shí)驗(yàn)分別用逐步接枝法和一步接枝法來將2.5G PAMAM接枝到氨基化Fe304上,并用水合肼改性端基為肼基(-NH-NH2),得到的復(fù)合粒子(Fe304-PAMAM-H)可以作為負(fù)載阿霉素的載體。表征結(jié)果表明：兩種方法均有PAMAM接枝到磁性粒子上,表面接枝并未改變Fe304磁性粒子的晶型,且一步接枝法得到的復(fù)合粒子表面接枝更多,體外細(xì)胞毒性低,可以被視為安全的藥物載體。4.阿霉素通過pH敏感的腙鍵負(fù)載到磁性納米樹枝狀大分子載體上,制備出pH敏感型磁靶向載藥體系。表征結(jié)果表明：一步接枝法制備出的Fe304-PAMAM-H具有比較高的載藥率和包封率,且載藥體系藥物的釋放對pH敏感,能有效的殺死腫瘤細(xì)胞。
[Abstract]:In recent years, intelligent responsive nanopharmaceuticals have attracted wide attention in drug release control systems. It is of great significance to control the drug release rate and reduce the side effects of drugs. However, the small changes of pH in different microenvironments of human tissues (the pH value of normal tissue cells is close to neutral, while the pH value of pathological tissue cells is between 5.5-6.9), pH response intelligent target drugs gradually become the focus of attention. In this paper, a pH sensitive magnetic targeting nano-carrier with good dispersion and low cytotoxicity in vitro was prepared and its drug loading properties were studied. The main work is as follows: 1. Poly (amide-amine) (PAMAM) dendrimers of 0.5G to 2.5G were prepared by divergence method. According to the yield and purity of the product, the optimum conditions for the synthesis of PAMAM were obtained as follows: optimum temperature 25 鈩，

本文編號：2270984