【摘要】：目前,治療癌癥的藥物分子一般水溶性還是比較差,因為作用于生物體內(nèi),生物可降解性、生物相容性和生物體內(nèi)的理化性質(zhì)穩(wěn)定性的表現(xiàn)變得尤為重要,同時糟糕的是治療癌癥的藥物分子對正常的組織器官以及正常的細胞的殺傷力也比較大,造成相當大的的毒副作用,所以兩親性藥物載體研究的應運而生也就在意料之中。目前,比較理想的藥物載體材料都具備多種性質(zhì),比如較高的載藥性、極低的毒性。隨著研究的加深,兩親性藥物載體也越來越完善化,目前較好的兩親性藥物載體作用原理是藥物與疏水部分的作用力將藥物包裹在內(nèi)殼里,親水段將藥物與外界分開,這樣不僅增加了藥物在體內(nèi)的溶解度,保證膠束的載藥量的,使其能夠有效地進入病灶部位,極大降低毒副作用,同時也增加了藥物的療效。本研究也是對兩親性藥物載體的開發(fā),同大多數(shù)藥物載體一樣,藥物載體由親水和疏水兩部分組成,在一定的濃度下形成穩(wěn)定的膠束體系,選取平均分子量為3000的聚乙二醇(PEG)為親水基團,以4-溴丁酸為底物所合成的長鏈化合物4-巰基丁酸接合喜樹堿(CPT)作為疏水基部分,合成兩親性藥物載體PEG-BRO-CPT,形成對稱結構,相對于其它類型的藥物載體,擁有載藥量更大、作用時間更長、毒性小、副作用更弱等優(yōu)良的性能。通過氫譜、碳譜對高分子化合物的結構進行表征,通過飛行質(zhì)譜對分子量進行計算。利用最直觀的熔點儀測定出載體膠束的最低臨界溶解溫度(LCST)是52.8℃。使用芘探針法繪制兩親性藥物載體PEG-BRO-CPT的臨界膠束濃度(CMC)數(shù)值是146 mg/L;通過動態(tài)光散射儀(DLS)掃描出膠束粒經(jīng)的大小為87 nm,Zeta電位值為-7.29。此外,通過還原性谷胱甘肽(GSH)對藥物載體進行體外模擬控釋實驗,有著不俗的表現(xiàn),從結構表征結果上看,兩親性藥物載體PEG-BRO-CPT作為對稱的4支鏈藥物載體,雖然在合成過程上略顯繁瑣與困難,但最終合成成功,相對于1支或2支的藥物載體的載藥量確實擁有巨大的提升。
[Abstract]:At present, the molecules that treat cancer are generally poor in water solubility, because the performance of biodegradability, biocompatibility and physical and chemical properties in organisms becomes particularly important. At the same time, what is worse is that the drug molecules that treat cancer also have great killing power to normal tissues and organs and normal cells, causing considerable toxic side effects, so the study of amphiphilic drug carriers is expected to emerge as the times require. At present, the ideal drug carrier materials have a variety of properties, such as high drug loading, very low toxicity. With the deepening of the research, amphiphilic drug carriers are becoming more and more perfect. At present, the better action principle of amphiphilic drug carriers is that the drugs are wrapped in the inner shell by the force of the drug and the hydrophobic part, and the hydrophilic segment separates the drug from the outside. This not only increases the solubility of the drug in vivo, but also ensures the drug loading of the micelle, which can effectively enter the focus, greatly reduce the toxic side effects, and increase the efficacy of the drug at the same time. Like most drug carriers, drug carriers are composed of hydrophilic and hydrophobic components, forming a stable micelle system at a certain concentration. Polyethylene glycol (PEG) with average molecular weight of 3000 was selected as hydrophilic group, and 4-mercaptobutyric acid (4-mercaptobutyric acid), a long chain compound, was synthesized by using 4-mercaptobutyric acid (4-mercaptobutyric acid) as hydrophobic group. The synthesis of amphiphilic drug carrier PEG-BRO-CPT, forms a symmetrical structure. Compared with other drug carriers, it has better properties such as larger drug load, longer action time, less toxicity and weaker side effects. The structure of polymer was characterized by hydrogen spectrum and carbon spectrum, and molecular weight was calculated by FMS. The minimum critical solution temperature (LCST) of the carrier micelles was determined by the most direct melting point analyzer at 52.8 鈩，

本文編號：2395567