两亲性药物载体PEG-BRO-CPT的合成及性能研究
发布时间：2018-12-30 12:11
【摘要】：目前,治疗癌症的药物分子一般水溶性还是比较差,因为作用于生物体内,生物可降解性、生物相容性和生物体内的理化性质稳定性的表现变得尤为重要,同时糟糕的是治疗癌症的药物分子对正常的组织器官以及正常的细胞的杀伤力也比较大,造成相当大的的毒副作用,所以两亲性药物载体研究的应运而生也就在意料之中。目前,比较理想的药物载体材料都具备多种性质,比如较高的载药性、极低的毒性。随着研究的加深,两亲性药物载体也越来越完善化,目前较好的两亲性药物载体作用原理是药物与疏水部分的作用力将药物包裹在内壳里,亲水段将药物与外界分开,这样不仅增加了药物在体内的溶解度,保证胶束的载药量的,使其能够有效地进入病灶部位,极大降低毒副作用,同时也增加了药物的疗效。本研究也是对两亲性药物载体的开发,同大多数药物载体一样,药物载体由亲水和疏水两部分组成,在一定的浓度下形成稳定的胶束体系,选取平均分子量为3000的聚乙二醇(PEG)为亲水基团,以4-溴丁酸为底物所合成的长链化合物4-巯基丁酸接合喜树碱(CPT)作为疏水基部分,合成两亲性药物载体PEG-BRO-CPT,形成对称结构,相对于其它类型的药物载体,拥有载药量更大、作用时间更长、毒性小、副作用更弱等优良的性能。通过氢谱、碳谱对高分子化合物的结构进行表征,通过飞行质谱对分子量进行计算。利用最直观的熔点仪测定出载体胶束的最低临界溶解温度(LCST)是52.8℃。使用芘探针法绘制两亲性药物载体PEG-BRO-CPT的临界胶束浓度(CMC)数值是146 mg/L;通过动态光散射仪(DLS)扫描出胶束粒经的大小为87 nm,Zeta电位值为-7.29。此外,通过还原性谷胱甘肽(GSH)对药物载体进行体外模拟控释实验,有着不俗的表现,从结构表征结果上看,两亲性药物载体PEG-BRO-CPT作为对称的4支链药物载体,虽然在合成过程上略显繁琐与困难,但最终合成成功,相对于1支或2支的药物载体的载药量确实拥有巨大的提升。
[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，
本文编号：2395567
[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，
本文编号：2395567
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