摘要：肿瘤是目前威胁全球人类健康和生命的第二大杀手，仅次于心脑血管疾病。治疗的肿瘤重要疗法之一是化学治疗，但在化疗过程中药物会对正常细胞和脏器产生毒害作用。因此，本课题以高效、低毒、靶向肿瘤组织的治疗为目的，利用肿瘤组织和肿瘤细胞内部特殊的偏酸性微环境特点，采用逆向蒸发法制备脂质体，从而构建新型、智能、靶向肿瘤细胞的脂质体递药系统旨在提高脂质体递药系统的肿瘤微环境敏感性能，改善药物释放行为，提高药效，减少毒副作用；同时在脂质体表面进行修饰，筛选出最佳膜材比；包载抗肿瘤模型药阿霉素，并对其在磷酸盐缓冲液中的体外释放进行考察；最后再对该递药系统的细胞药效进行初步评价。结果显示：膜材蛋黄卵磷脂与胆固醇的摩尔比为4:1，多肽材料为所有膜材料（蛋黄卵磷脂+胆固醇）摩尔比的1:50时， pH敏感性最好，能受低pH值触发，快速释药，提高药效； CCK-8法的细胞实验结果证实，GALA修饰后的脂质体给药组对乳腺癌上皮细胞的生长抑制作用明显提高。33889
毕业论文关键词：肿瘤微环境；脂质体纳米递药系统；阿霉素；GALA
Preparation and preliminary evaluation of liposomes responsing in the tumor microenvironment
Abstract: Tumor is a global threat to human health and life, the second largest killer listed after cardiovascular disease. One of the important tumor therapeutic method is chemotherapy, but chemotherapy drugs have toxic effects on normal cells and tissues. Therefore, this paper aims atdeveloping an more efficient, lower toxicity and targeted drug delivery system withthe sensitive capability to acidic microenvironment . Liposome was prepared by reverse-phase evaporation with the modified surface of the liposome. select the best membrane ratio; entrapped anti-tumor drug adriamycin model, and its in vitro release in phosphate buffer to inspect; and finally the delivery system of the cell preliminary evaluation of efficacy. This study aims to improve liposome delivery system tumor microenvironment sensitive performance, improving drug release behavior, improve efficacy, reduce side effects. The results show that: the molar ratio of membrane cholesterol egg yolk lecithin and 4: 1, the polypeptide GALA entire membrane material (yolk lecithin + cholesterol) 1:50, at low pH in the only sensitive; The results cell by CCK-8 confirmed, GALA modified liposome administration group growth inhibition of breast cancer epithelial cells was significantly increased.
Keywords: tumor microenvironment; Nano liposome delivery systems; doxorubicin; GALA
目录
1. 前言 1
1.1 肿瘤及其治疗现状 1
1.2 模型药物阿霉素 1
1.3 脂质体递药系统研究进展 1
1.4 肿瘤微环境 2
1.5 GALA多肽 2
2. 材料和仪器 4
2.1 材料 4
2.2 仪器 4
2.3 主要试剂的配制 5
3. 实验方法 7
3.1 功能性膜材料的表征与评价 7
3.1.1 GALA-SA的纯度检测 7
3.1.2 GALA-SA的质谱检测 7
3.1.3 GALA-SA的pH敏感性评价 7
3.2 脂质体递药系统的处方工艺筛选及其评价 7
3.2.1 阿霉素水溶液标准曲线的绘制 7
3.2.2 阿霉素酸性异丙醇溶液标准曲线的绘制 7
3.2.3 脂质体的制备方法及其载药温度的优化 8
3.2.4 普通脂质体处方比的筛选 8
3.2.5 GALA修饰脂质体递药系统的处方比筛选 8
3.2.6 GALA修饰脂质体递药系统的功能性评价 9 肿瘤微环境响应的脂质体制备及初步评价:http://www.751com.cn/yixue/lunwen_31200.html