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

【摘要】：藥物遞送系統(tǒng)在醫(yī)學(xué)和藥學(xué)領(lǐng)域受到越來(lái)越多的關(guān)注,因?yàn)樗梢源蠓岣吒鞣N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(yīng)型藥物遞送系統(tǒng)可以減少藥物在遞送過(guò)程中的降解,在血液循環(huán)過(guò)程中增加藥物在腫瘤部位的堆積,達(dá)到在時(shí)間上和空間上釋放藥物的效果,同時(shí)可以減少藥物對(duì)正常細(xì)胞的傷害。光響應(yīng)型材料受到人們?cè)絹?lái)越多的關(guān)注,因?yàn)樵诖碳ば砸蛩刂泄馐亲钣邢Ｍ倪x擇,它可以通過(guò)改變光照時(shí)間、光照強(qiáng)度以及光束直徑來(lái)控制藥物的釋放。基因治療是一種將基因遞送到細(xì)胞或組織用于遺傳性疾病治療的技術(shù),目前已經(jīng)廣泛應(yīng)用于癌癥和傳染性疾病的治療。PEI是一種陽(yáng)離子聚合物,由于其氨基基團(tuán)較多,PEI的表面正電荷也較多,因此容易與帶負(fù)電荷較多的分子如DNA因靜電相互作用結(jié)合。而且它還可以通過(guò)破壞溶酶體膜進(jìn)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(shí)驗(yàn)。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(huì)相應(yīng)增加。為了提高轉(zhuǎn)染效率同時(shí)降低毒性,很多課題組對(duì)分子量較小的PEI進(jìn)行了修飾,達(dá)到提高轉(zhuǎn)染效率的目的。一、本文設(shè)計(jì)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(tuán)兩種光敏基團(tuán),與乙醇胺和二甲基丙烯酰氯反應(yīng)得到聚酯,通過(guò)乳液聚合的方法制備了光敏性的納米粒。同時(shí),為了考察它們的光致釋放效應(yīng),將姜黃素和lapachone包載在納米粒中。本文對(duì)納米粒進(jìn)行了紫外可見(jiàn)光譜(UV-Vis)、動(dòng)態(tài)光散射(DLS)和掃描電鏡的表征,同時(shí)考察了納米粒在細(xì)胞內(nèi)的攝取和光控釋放能力。通過(guò)對(duì)這些性能的研究,本文得出結(jié)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(huì)增大,但是不會(huì)增大很多,同時(shí)可以釋放包封的藥物,達(dá)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(dāng)分子量較大的聚合物PEI-CL進(jìn)入細(xì)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(shí)提高其轉(zhuǎn)染效率。我們?cè)O(shè)計(jì)了PEI-CL聚合物,并使用紅外光譜進(jìn)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(xué)位授予單位】：河北大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：TB383.1;TQ460.1

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