本文選題：溫度敏感水凝膠 + PEG-PELG　； 參考：《吉林大學(xué)》2017年碩士論文

【摘要】：目的:癌癥作為一種世界范圍內(nèi)的公共衛(wèi)生問題,是造成人類死亡的第二大死因,其具有廣泛的發(fā)病范圍、逐年升高的死亡率,嚴(yán)重威脅人類的健康�；熓悄壳胺鞘中g(shù)治療癌癥的重要方法,但存在注射頻率高、藥物利用率低、體內(nèi)代謝迅速、毒副作用大等缺點(diǎn),使其治療效果無(wú)法達(dá)到預(yù)期。溫度敏感水凝膠作為藥物載體具有良好的生物可降解性和組織相容性,應(yīng)用于腫瘤局部治療具有提高局部藥物濃度、藥物緩釋(長(zhǎng)效性)、給藥頻率低,機(jī)體毒性小等優(yōu)點(diǎn),作為藥物載體已廣泛用于腫瘤的局部治療研究中。藥物聯(lián)合治療是增強(qiáng)治療效果的有效途徑,目前常用的聯(lián)合治療方案包括手術(shù)/化療,化療/放療、化療/免疫治療以及多種化療藥物聯(lián)用等均可明顯提高治療效果。聚乙二醇-聚(γ-乙基-L-谷氨酸酯)(PEG-PELG)水凝膠作為新型的溫度敏感型水凝膠,在體內(nèi)可以快速成膠,并作為可注射材料為藥物緩釋提供載體。本研究的目的是探索這種水凝膠材料共擔(dān)載組蛋白去乙�；敢种苿┍焖徕c(sodium valproate,VPA)與抗腫瘤化療藥順鉑(cis-platinum,CDDP)后對(duì)耐藥細(xì)胞株的殺傷效果,為進(jìn)一步研究及臨床應(yīng)用提供依據(jù)。具體方案如下:利用開環(huán)聚合方法制備二嵌段聚合物PEG-PELG并進(jìn)行性狀表征以確定其聚合度和分子量得到具體結(jié)構(gòu)PEG2K-PELG15,其成膠溫度隨濃度的增高而降低,丙戊酸鈉和順鉑聯(lián)用細(xì)胞毒性實(shí)驗(yàn)表明兩藥聯(lián)用后可提高對(duì)A549/CDDP細(xì)胞抗腫瘤效果,誘導(dǎo)細(xì)胞凋亡和細(xì)胞周期阻滯,利用物理混勻的方法擔(dān)載VPA和CDDP后,細(xì)胞毒性實(shí)驗(yàn)表明聯(lián)合載藥后可提高對(duì)耐藥細(xì)胞A549/CDDP抗腫瘤效果,表明PEG2K-PELG15作為藥物緩釋載體聯(lián)合擔(dān)載VPA和CDDP后可提高A549/CDDP的治療效果,并降低A549/CDDP腫瘤耐藥性,在肺癌治理中具有良好的應(yīng)用前景。綜上所述,溫度敏感水凝膠PEG-PELG具有良好的生物相容性、生物可降解性和藥物緩釋性能,擔(dān)載藥物后在腫瘤局部治療中具有良好的應(yīng)用前景。丙戊酸鈉作為組蛋白去乙�；敢种苿┡c化療藥順鉑聯(lián)合使用具有協(xié)同抑制腫瘤細(xì)胞的能力,在腫瘤體外探索實(shí)驗(yàn)中具有潛在的研究?jī)r(jià)值。
[Abstract]:Objective: cancer, as a worldwide public health problem, is the second leading cause of human mortality. Cancer has a wide range of morbidity and increases year by year, which is a serious threat to human health. Chemotherapy is an important method for non-surgical treatment of cancer at present, but there are some disadvantages such as high injection frequency, low utilization rate of drugs, rapid metabolism in vivo and large toxic side effects, which make the therapeutic effect unattainable. Thermosensitive hydrogel as a drug carrier has good biodegradability and histocompatibility. The application of thermo-sensitive hydrogel in tumor local treatment has the advantages of increasing local drug concentration, drug release (long-term effect), low administration frequency, low toxicity, and so on. As a drug carrier, it has been widely used in the study of local treatment of tumor. Drug combination therapy is an effective way to enhance the therapeutic effect. At present, the commonly used combination treatment schemes include surgery / chemotherapy, chemotherapy / radiotherapy, chemotherapy / immunotherapy and the combination of various chemotherapeutic drugs. As a new type of temperature sensitive hydrogel, PEG-PELG hydrogel can be used as injectable material for drug delivery. The aim of this study was to explore the killing effect of sodium valproate and cis-platinum cisplatin (cis-platinum CDDP), a hydrogel material, on drug-resistant cell lines, and to provide evidence for further study and clinical application. The specific scheme is as follows: the diblock polymer PEG-PELG was prepared by ring-opening polymerization and its properties were characterized to determine its polymerization degree and molecular weight to obtain a specific structure PEG2K-PELG15, and the gelation temperature decreased with the increase of the concentration of PEG-PELG. The cytotoxicity test of sodium valproate and cisplatin showed that the combination of the two drugs could improve the anti-tumor effect, induce apoptosis and cell cycle arrest of A549% CDDP cells. VPA and CDDP were loaded by physical mixing method. Cytotoxicity test showed that combined drug loading could improve the anti-tumor effect of A549% CDDP on resistant cells, which indicated that PEG2K-PELG15 combined with VPA and CDDP as drug sustained-release carrier could increase the therapeutic effect of A549% CDDP and reduce the drug resistance of A549% CDDP tumor. It has a good application prospect in the treatment of lung cancer. In conclusion, PEG-PELG has good biocompatibility, biodegradability and drug release properties. Sodium valproate as a histone deacetylase inhibitor combined with cisplatin has a synergistic ability to inhibit tumor cells and has potential research value in tumor exploration in vitro.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R943;R96

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相關(guān)期刊論文 前2條

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本文編號(hào)：2112056