本文選題：藥物傳輸　切入點(diǎn)：納米粒子　出處：《長(zhǎng)春工業(yè)大學(xué)》2017年碩士論文

【摘要】：在過(guò)去的幾十年里,已經(jīng)研發(fā)了許多種環(huán)境敏感的聚合物納米粒子(NPs)用作腫瘤靶向傳輸抗腫瘤藥物的智能納米載體。臨床和預(yù)臨床研究已經(jīng)表明,聚合物納米載體能夠延長(zhǎng)體內(nèi)的循環(huán)時(shí)間,通過(guò)增強(qiáng)滲透和滯留(EPR)效應(yīng)特定靶向到腫瘤組織,并減少藥物的毒副作用,從而提高治療效率。由于與正常組織相比,腫瘤細(xì)胞具有特定的腫瘤微環(huán)境,所設(shè)計(jì)的納米載體通常能夠在血液循環(huán)中穩(wěn)定存在,一旦在腫瘤部位或細(xì)胞內(nèi)空間遇到生物刺激,便能響應(yīng)性地釋放所擔(dān)載物。在這些情況下,人們廣泛研究了各種響應(yīng)性刺激,如pH,谷胱甘肽(GSH),溫度,光和酶。為了研發(fā)應(yīng)用于藥物傳輸系統(tǒng)的刺激敏感性材料,已經(jīng)將多種功能和刺激響應(yīng)部分與具有良好生物相容性及生物降解性的不同聚合物相結(jié)合。葡聚糖是親水性多糖,已經(jīng)廣泛應(yīng)用于構(gòu)建納米粒子藥物傳輸系統(tǒng)�？鼓[瘤藥物可以直接鍵合到葡聚糖的骨架上,也可以包載到葡聚糖構(gòu)建的疏水核膠束中,用于全身藥物傳輸系統(tǒng)。然而,很少有關(guān)于核交聯(lián)葡聚糖用于抗腫瘤傳輸系統(tǒng)的報(bào)道。pH和還原雙重敏感的納米粒子廣泛應(yīng)用于刺激響應(yīng)藥物載體,用來(lái)改善抗癌藥物在細(xì)胞內(nèi)的傳輸。如何在提高載藥效率的同時(shí)降低毒副作用,如何實(shí)現(xiàn)藥物在正常生理?xiàng)l件下少量釋放,同時(shí)在細(xì)胞內(nèi)條件下快速釋放等仍是需要解決的問(wèn)題。本文通過(guò)簡(jiǎn)單的化學(xué)交聯(lián)方法制備了一種聚乙二醇接枝葡聚糖納米粒子(CPD NPs),用于pH與還原雙響應(yīng)藥物傳輸體系。所得到的CPD納米粒子是均勻的球形結(jié)構(gòu),粒徑大小在69 nm至107 nm之間。隨后將抗腫瘤藥物阿霉素高效擔(dān)載到CPD納米粒子中,通過(guò)體外釋放實(shí)驗(yàn),說(shuō)明該載藥體系具有還原及pH雙重響應(yīng)性。流式細(xì)胞術(shù)和共聚焦顯微鏡結(jié)果證明載阿霉素的CPD納米粒子可以有效的進(jìn)入到細(xì)胞內(nèi),并且能夠在細(xì)胞微環(huán)境中成功釋放阿霉素。另外,細(xì)胞毒性實(shí)驗(yàn)顯示,CPD納米粒子對(duì)于正常細(xì)胞以及腫瘤細(xì)胞均具有很好的生物相容性,而且載阿霉素的CPD納米粒子能夠明顯抑制多種腫瘤細(xì)胞的細(xì)胞增殖。因此,在腫瘤的臨床治療中,該種生物相容的CPD納米粒子擁有巨大潛力應(yīng)用于細(xì)胞內(nèi)藥物傳輸系統(tǒng)。
[Abstract]:In the past few decades, many kinds of environment-sensitive polymer nanoparticles (NPs) have been developed as intelligent nano-carriers for tumor targeted delivery of anti-tumor drugs. Clinical and pre-clinical studies have shown that. Polymer nanocarriers can prolong the circulation time in vivo, target tumor tissues by enhancing the effect of osmotic and retention EPRs, and reduce the toxic and side effects of drugs, thus improving the therapeutic efficiency. Tumor cells have a specific tumor microenvironment, and the designed nano-carriers usually exist stably in the blood circulation, once the biological stimulation is encountered in the tumor site or in the cell space. In these cases, a wide range of responsive stimuli, such as pH, glutathione glutathione GSH, temperature, light and enzymes, have been studied in order to develop stimulus-sensitive materials for use in drug delivery systems. Multiple functions and stimuli have been combined with different polymers with good biocompatibility and biodegradability. Dextran is a hydrophilic polysaccharide. Antitumor drugs can be directly bonded to the skeleton of dextran or encapsulated into the hydrophobic nuclear micelles constructed by dextran for use in a systemic drug delivery system. Few reports on the use of nuclear crosslinked dextran in antitumor transport systems. Ph and reductive dual sensitive nanoparticles have been widely used in stimulus-responsive drug carriers. To improve the delivery of anticancer drugs in cells. How to improve the efficiency of drug delivery while reducing side effects, how to achieve a small amount of drug release under normal physiological conditions, At the same time, rapid release in intracellular condition is still a problem to be solved. In this paper, a kind of polyethylene glycol grafted dextran nanoparticles (CPD NPsN) was prepared by simple chemical crosslinking method, which was used for pH and reduction double response drug transport. System. The obtained CPD nanoparticles are spherical in structure. The particle size ranged from 69 nm to 107 nm. The antitumor drug doxorubicin was then loaded into CPD nanoparticles and released in vitro. The results of flow cytometry and confocal microscopy showed that the CPD nanoparticles loaded with doxorubicin could effectively enter the cells. In addition, cytotoxicity tests show that CPD nanoparticles have good biocompatibility for both normal cells and tumor cells. Moreover, CPD nanoparticles loaded with adriamycin can significantly inhibit the proliferation of various tumor cells. Therefore, the biocompatible CPD nanoparticles have great potential to be used in intracellular drug delivery systems in the clinical treatment of tumors.
【學(xué)位授予單位】：長(zhǎng)春工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：TQ460.1;TB383.1

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相關(guān)期刊論文 前1條

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本文編號(hào)：1659782