摘要
目的本研究将丁酸与5-氨基水杨酸(5-aminosalicylic acid,5-ASA)通过化学反应合成2-丁酰氧基-5-丁酰胺基苯甲酸(2-butyloxide-5-butylaminobenzoic acid,BBA),作为治疗结肠癌的前体药物,利用纳米技术制备BBA纳米晶缓控释制剂,并探讨BBA纳米晶对结肠癌细胞的抑制作用。方法采用溶剂反溶剂沉淀法制备BBA纳米晶,通过核磁共振扫描、红外光谱仪和透射电镜等进行物理化学表征;使用高效液相色谱法检测含量;并通过MTT实验检测不同浓度的BBA、BBA纳米晶、空白纳米晶、5-氟尿嘧啶、5-氨基水杨酸和丁酸钠与结肠癌细胞SW620共同孵育24、48、72 h后细胞的存活率,以探索BBA纳米晶对结肠癌细胞SW620的抑制效果。结果本实验成功制备了BBA纳米晶。MTT结果显示,作用时间为24 h时,各个浓度条件下BBA纳米晶与BBA对结肠癌细胞SW620的抑制率较低,两组间差异无统计学意义(P>0.05);作用时间分别为48 h和72 h,药物浓度为30μm和40μm时,BBA纳米晶对结肠癌细胞SW620的体外抑制效果低于阳性对照5-氟尿嘧啶组,但明显优于其余各同浓度给药组;BBA纳米晶与BBA,两组间比较对结肠癌细胞SW620的抑制率差异有统计学意义(P<0.05),从而表明BBA纳米晶具有缓释性,并对结肠癌细胞SW620有较好的抑制作用。结论本研究成功制备了丁酸前药BBA纳米晶,并证明了该新型药物制剂对结肠癌细胞具有抑制作用,这一结果将为结肠癌的临床治疗提供新的思路和方法。
Objective In this study,2-butyloxide-5-butylaminobenzoic acid(BBA)was synthesized with butyric acid and 5-aminosalicylic acid,which can be used as the prodrug for the treatment of colon cancer.The sustained-release preparation of BBA nano-crystals expected with good targeting and high bioavailability was prepared by using nanotechnology,which could effectively solve the problems of antitumor drug solubility and pharmaceutical properties.Methods BBA nanocrystals were prepared by solvent-antisolvent precipitation,and were characterized by NMR scanning,infrared spectrometer and transmission electron microscopy.High-performance liquid chromatography(HPLC)was used to detect the content of BBA.The cell viability of SW620 cells treated with different concen-trations of BBA,BBA nanocrystals,blank nanocrystals,5-fluorouracil(5-FU),5-aminosalicylic acid(5-ASA)and sodium butyrate(NaB)were detected by MTT assay.Results BBA nanocrystals were successfully prepared.MTT results showed that the in vitro inhibi-tory effect of BBA nanocrystals on colon cancer cells of SW620 was slightly lower than that of the positive control group of 5-FU(P>0.05),but was similar to the other groups at the same concentration,indicating that BBA nanocrystals showed desire inhibitory effect on colon cancer cells SW620 in vitro(P<0.05).Conclusion In the present study,we successfully prepared the nanocrystals of BBA as the pro-drug of butyric,which proved that the new drug preparation showed an inhibitory effect on colon cancer cells,and might provide an extremely significant new idea and original approach for the clinical treatment of colon cancer.
作者
林燕
兰华琪
吕诺男
熊梦佳
王诚梽
吴越
孙小端
杜兴杰
刘中兵
钟志容
LIN Yan;LAN Huaqi;LV Nuonan;XIONG Mengjia;WANG Chengzhi;WU Yue;SUN Xiaoduan;DU Xingjie;LIU Zhongbing;ZHONG Zhirong(School of Pharmacy,Southwest Medical University,Luzhou 646000,China;Department of Pharmacy,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,China;Department of Pharmacy,The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646000,China)
出处
《西南医科大学学报》
2024年第2期123-129,共7页
Journal of Southwest Medical University
基金
四川省科技厅项目(2022YFS0627,2022YFS0188)
泸州市科技计划项目(2023JYJ023)
大学生创新创业训练计划(202310632075,202210632003)
教育部‘春晖计划’合作科研项目(202200618)。
关键词
结肠癌
丁酸
5-氨基水杨酸
纳米晶
Colon cancer
Butyric acid
5-Aminosalicylic acid
Nanocrystals
