本文選題：藥物遞送系統(tǒng) + 光敏性　； 參考：《河北大學》2017年碩士論文

【摘要】：藥物遞送系統(tǒng)在醫(yī)學和藥學領域受到越來越多的關注,因為它可以大幅提高各種治療方案的效率。與傳統(tǒng)的腫瘤治療方法(化療)相比,建立刺激響應型藥物遞送系統(tǒng)可以減少藥物在遞送過程中的降解,在血液循環(huán)過程中增加藥物在腫瘤部位的堆積,達到在時間上和空間上釋放藥物的效果,同時可以減少藥物對正常細胞的傷害。光響應型材料受到人們越來越多的關注,因為在刺激性因素中光是最有希望的選擇,它可以通過改變光照時間、光照強度以及光束直徑來控制藥物的釋放�；蛑委熓且环N將基因遞送到細胞或組織用于遺傳性疾病治療的技術,目前已經(jīng)廣泛應用于癌癥和傳染性疾病的治療。PEI是一種陽離子聚合物,由于其氨基基團較多,PEI的表面正電荷也較多,因此容易與帶負電荷較多的分子如DNA因靜電相互作用結合。而且它還可以通過破壞溶酶體膜進而從內(nèi)涵體中逃逸,因此PEI被成功的用于體內(nèi)和體外的基因遞送實驗。研究證明,隨著分子量的增大,PEI的轉(zhuǎn)染效率隨之增大,但是毒性也會相應增加。為了提高轉(zhuǎn)染效率同時降低毒性,很多課題組對分子量較小的PEI進行了修飾,達到提高轉(zhuǎn)染效率的目的。一、本文設計了兩種可以光致降解的藥物遞送系統(tǒng)。本文使用鄰硝基卞醇和香豆素基團兩種光敏基團,與乙醇胺和二甲基丙烯酰氯反應得到聚酯,通過乳液聚合的方法制備了光敏性的納米粒。同時,為了考察它們的光致釋放效應,將姜黃素和lapachone包載在納米粒中。本文對納米粒進行了紫外可見光譜(UV-Vis)、動態(tài)光散射(DLS)和掃描電鏡的表征,同時考察了納米粒在細胞內(nèi)的攝取和光控釋放能力。通過對這些性能的研究,本文得出結論,利用聚乙二醇二甲基丙烯酸酯作為交聯(lián)劑,光照之后納米粒粒徑會增大,但是不會增大很多,同時可以釋放包封的藥物,達到一定的治療效果。二、本文使用二硫化物作為交聯(lián)劑將分子量較小的PEI連接成分子量較大的聚合物,當分子量較大的聚合物PEI-CL進入細胞后,二硫鍵在谷胱甘肽還原酶的作用下斷裂,分子量減小,毒性隨之減小,同時提高其轉(zhuǎn)染效率。我們設計了PEI-CL聚合物,并使用紅外光譜進行表征,并考察了它的轉(zhuǎn)染效率。PEI-CL的轉(zhuǎn)染效率明顯高于PEI 1.8K。
[Abstract]:Drug delivery systems have received increasing attention in the medical and pharmaceutical fields because they can greatly improve the efficiency of various treatment schemes. Compared with traditional cancer therapy (chemotherapy), the establishment of stimulus-responsive drug delivery systems can reduce the degradation of drugs during delivery and increase the accumulation of drugs in tumor sites during blood circulation. Achieve the effect of releasing drugs in time and space, while reducing damage to normal cells. More and more attention has been paid to photo-responsive materials, because light is the most promising choice among the stimulative factors, which can control the release of drugs by changing the illumination time, light intensity and beam diameter. Gene therapy is a technology that delivers genes to cells or tissues for the treatment of genetic diseases. PEI is a cationic polymer that has been widely used in the treatment of cancer and infectious diseases. Because the amino groups of PEI have more positive surface charges, it is easy to interact with the negatively charged molecules such as DNA because of electrostatic interaction. And it can escape from the connotations by destroying the lysosomal membrane, so PEI has been successfully used in gene delivery experiments in vivo and in vitro. The results showed that the transfection efficiency of PEI increased with the increase of molecular weight, but the toxicity also increased. In order to improve the transfection efficiency and reduce the toxicity, many research groups modified PEI with small molecular weight to improve the transfection efficiency. First, two photodegradable drug delivery systems are designed. In this paper, two kinds of Guang Min groups, o-nitrobenol and coumarin, were used to react with ethanolamine and dimethacryloyl chloride to obtain polyester. Guang Min nanoparticles were prepared by emulsion polymerization. At the same time, curcumin and lapachone were encapsulated in nanoparticles to investigate their photo-release effects. The ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS) and scanning electron microscopy (SEM) were used to characterize the nanoparticles. Through the study of these properties, it is concluded that the size of the nanoparticles will increase after irradiation with polyethylene glycol dimethacrylate as crosslinking agent, but it will not increase much, and the encapsulated drugs can be released at the same time. To achieve a certain therapeutic effect. Secondly, using disulfide as crosslinking agent, PEI with small molecular weight was connected to polymer with high molecular weight. When PEI-CL, a polymer with higher molecular weight, entered the cell, the disulfide bond broke down under the action of glutathione reductase, and the molecular weight decreased. The toxicity decreased and the transfection efficiency was improved. PEI-CL polymer was designed and characterized by infrared spectroscopy. The transfection efficiency of PEI-CL was significantly higher than that of PEI 1.8K.
【學位授予單位】：河北大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：TB383.1;TQ460.1

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