pH敏感型基因及藥物載體的制備及其性能研究
發(fā)布時間：2018-08-15 19:39
【摘要】：隨著分子生物學及其相關學科的不斷發(fā)展,針對傳統(tǒng)治療手段難以治愈的基因缺陷等疾病及傳統(tǒng)藥物治療的毒副作用較大的問題,分別提出了基因治療及靶向藥物治療的概念。而實現基因治療及靶向藥物治療均離不開載體材料。本研究通過利用r-氨丙基三乙氧基硅烷(APTES)及其水解產物八臂氨基多面體硅氧烷(PNH)作為引導劑,分別制備得到了兩類不同的載體材料,并對其相關性能進行研究。利用r-氨丙基三乙氧基硅烷(APTES)中氨基基團的正電性,及其與鈣離子的結合特性,通過引導鈣離子與碳酸根離子結合形成的碳酸鈣納米粒,并改變制備工藝條件,制備得到了不同形貌的碳酸鈣載體材料,同時對其制備工藝原理進行相關探究。選擇已制備的棒狀碳酸鈣粒子作為抗癌藥物阿霉素載體,對其負載阿霉素藥物前后的生物學性能、載藥及藥物釋放性能進行研究。同時,選擇制備的碳酸鈣微球作為Osterix基因的轉染載體,并對其相關性能進行研究。通過研究發(fā)現,棒狀碳酸鈣粒子作為阿霉素藥物載體時,具有較高的藥物負載性能。同時通過實驗設計,實現其藥物釋放速率能夠對藥物載體所在釋放環(huán)境的p H值具有顯著的響應性。研究發(fā)現,所設計的負載藥物的載體材料能夠實現在中性條件下藥物釋放速率的顯著降低。作為基因載體去實現基因轉染的實驗研究發(fā)現球形碳酸鈣材料(r CCMP)能夠實現一定的轉染效率,具有作為基因轉染載體材料的潛力。選取具有較好生物相容性的聚己內酯(PCL)作為主體材料,通過天冬氨酸(Asp)修飾PCL端基,然后與PNH進行分子自組裝。通過分子自組裝的方法制備了尺寸均一、較好分散性和較低生物毒性的PCL-Asp/PNH微球材料。利用制備得到的微球負載阿霉素藥物,并對其藥物負載能力及其在PBS緩沖液中的藥物釋放性能進行相關研究。研究發(fā)現,PCL-Asp/PNH微球載體材料對阿霉素藥物的藥物負載率在設計的條件下能夠達到77.58%,且其在酸性條件下能夠實現藥物的持續(xù)釋放。5天內的藥物釋放率達到77.16%,能夠實現一定的緩釋作用,但其在中性的PBS環(huán)境下,藥物的釋放率較低(不到20%)。
[Abstract]:With the development of molecular biology and its related disciplines, the concepts of gene therapy and targeted drug therapy have been put forward for diseases such as gene defects which can not be cured by traditional treatment methods and the large toxicity and side effects of traditional drug therapy. Both gene therapy and targeted drug therapy can not be achieved without carrier materials. In this study, two kinds of different carrier materials were prepared by using r-aminopropyltriethoxysilane (APTES) and its hydrolysate octa-arm aminopolyhedral siloxane (PNH) as the guiding agent, and their related properties were studied. According to the positive charge of amino group in r-aminopropyl triethoxy silane (APTES) and its binding property with calcium ion, calcium carbonate nanoparticles were formed by guiding calcium ion to combine with carbonate ion, and the preparation conditions were changed. Calcium carbonate carrier materials with different morphologies were prepared, and the preparation principle of calcium carbonate was studied. Rod calcium carbonate particles were selected as the carrier of adriamycin to study the biological properties, drug loading and drug release before and after loading adriamycin. At the same time, calcium carbonate microspheres were selected as the transfection vector of Osterix gene, and the related properties were studied. It was found that the rod-shaped calcium carbonate particles had high drug loading performance when they were used as drug carriers for doxorubicin. At the same time, the experimental design shows that the drug release rate can be significantly responsive to the pH value of the release environment where the drug carrier is located. It is found that the designed carrier material can significantly reduce the drug release rate under neutral conditions. As a gene vector to realize gene transfection, it was found that the spherical calcium carbonate material (r CCMP) could achieve a certain transfection efficiency, and had the potential as a gene transfection vector material. Polycaprolactone (PCL) with good biocompatibility was selected as the main material. The PCL terminal group was modified by aspartic acid (Asp) and then self-assembled with PNH. PCL-Asp/PNH microspheres with uniform size, good dispersion and low biotoxicity were prepared by molecular self-assembly. Doxorubicin was loaded with microspheres and its drug loading capacity and drug release in PBS buffer were studied. The results show that the drug loading rate of PCL-AspP / PNH microspheres can reach 77.58 under the designed conditions, and the drug release rate of PCL-AspP / PNH microspheres can reach 77.16% within 5 days after sustained release under acidic conditions. The drug delivery rate of PCL-Aspp / PNH microspheres can reach 77.58 in the designed condition, and the drug release rate can reach 77.16% in acidic condition. A certain slow release effect, But in neutral PBS, the drug release rate was lower (less than 20%).
【學位授予單位】：華南理工大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R318.08
本文編號：2185206
[Abstract]:With the development of molecular biology and its related disciplines, the concepts of gene therapy and targeted drug therapy have been put forward for diseases such as gene defects which can not be cured by traditional treatment methods and the large toxicity and side effects of traditional drug therapy. Both gene therapy and targeted drug therapy can not be achieved without carrier materials. In this study, two kinds of different carrier materials were prepared by using r-aminopropyltriethoxysilane (APTES) and its hydrolysate octa-arm aminopolyhedral siloxane (PNH) as the guiding agent, and their related properties were studied. According to the positive charge of amino group in r-aminopropyl triethoxy silane (APTES) and its binding property with calcium ion, calcium carbonate nanoparticles were formed by guiding calcium ion to combine with carbonate ion, and the preparation conditions were changed. Calcium carbonate carrier materials with different morphologies were prepared, and the preparation principle of calcium carbonate was studied. Rod calcium carbonate particles were selected as the carrier of adriamycin to study the biological properties, drug loading and drug release before and after loading adriamycin. At the same time, calcium carbonate microspheres were selected as the transfection vector of Osterix gene, and the related properties were studied. It was found that the rod-shaped calcium carbonate particles had high drug loading performance when they were used as drug carriers for doxorubicin. At the same time, the experimental design shows that the drug release rate can be significantly responsive to the pH value of the release environment where the drug carrier is located. It is found that the designed carrier material can significantly reduce the drug release rate under neutral conditions. As a gene vector to realize gene transfection, it was found that the spherical calcium carbonate material (r CCMP) could achieve a certain transfection efficiency, and had the potential as a gene transfection vector material. Polycaprolactone (PCL) with good biocompatibility was selected as the main material. The PCL terminal group was modified by aspartic acid (Asp) and then self-assembled with PNH. PCL-Asp/PNH microspheres with uniform size, good dispersion and low biotoxicity were prepared by molecular self-assembly. Doxorubicin was loaded with microspheres and its drug loading capacity and drug release in PBS buffer were studied. The results show that the drug loading rate of PCL-AspP / PNH microspheres can reach 77.58 under the designed conditions, and the drug release rate of PCL-AspP / PNH microspheres can reach 77.16% within 5 days after sustained release under acidic conditions. The drug delivery rate of PCL-Aspp / PNH microspheres can reach 77.58 in the designed condition, and the drug release rate can reach 77.16% in acidic condition. A certain slow release effect, But in neutral PBS, the drug release rate was lower (less than 20%).
【學位授予單位】：華南理工大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R318.08
【參考文獻】
相關期刊論文 前2條
1 胡運玖;左奕;鄔均;李玉寶;孟純陽;王尖;蔣電明;;聚己內酯載藥微球的制備及釋藥性能研究[J];材料導報;2015年02期
2 于金剛;黃可龍;楊巧勤;劉素琴;唐金春;;碳納米管作為藥物載體的研究進展[J];藥學學報;2008年10期
相關博士學位論文 前1條
1 鄭蒙;基于低分子量聚乙烯亞胺的高效低毒基因載體[D];蘇州大學;2012年
相關碩士學位論文 前2條
1 昝曉麗;半乳糖修飾的殼聚糖-聚己內酯納米微球用于肝細胞靶向藥物釋放[D];華中科技大學;2010年
2 韓華鋒;碳酸鈣微球作為p53基因載體的研究[D];浙江理工大學;2014年
，本文編號：2185206
本文鏈接：http://sikaile.net/yixuelunwen/swyx/2185206.html
