替加氟-焦脱镁叶绿酸A胶束的制备

Preparation of Tegafur-pyropheophorbide Acid A Micelles

目的以替加氟和焦脱镁叶绿酸A为原料合成缀合物,并将其制备成胶束,实现光动力治疗和化疗的协同抗肿瘤作用。方法以丁二酸酐连接替加氟衍生物与焦脱镁叶绿酸A,通过核磁共振氢谱、质谱进行结构表征;通过溶剂挥发法制备载药胶束,以载药量、形貌、粒径、ζ电位、体外抗肿瘤活性等对载药胶束进行制剂学评价。结果替加氟-焦脱镁叶绿酸A复合物的结构得以确证;通过马尔文激光粒度仪和透射电镜验证所制备载药胶束粒径为143.9 nm,粒度均一;载药胶束可持续释药72 h以上,且激光照射可加速药物释放;载药胶束经激光照射可增强体外抗肿瘤效果,IC_(50)值为14.81μg·mL^(-1),其细胞毒性相较于单独给药替加氟增加至1.43倍。结论替加氟-焦脱镁叶绿酸A前药负载的胶束可实现替加氟的缓释作用,并可通过光动力治疗联合化疗有效提高替加氟体外抗肿瘤效果。

Objective To synthesize the conjugate of tegafur and pyropheophorbic acid A.It was loaded into micelles to achieve the synergistic of photodynamic therapy and chemotherapy for antitumor efficiency.Methods Succinic anhydride was used to link tegafur derivative and pyropheophorbic acid A and its structure was characterized by NMR and MS.The loaded micelles were prepared by the solvent evaporation and characterized by drug loading capacity,morphology,particle size,ζ potential as well as antitumor activity in vitro.Results The structure of conjugate was confirmed as desired.The particle size of loaded micelles was 143.9 nm,which was verified by Malvern laser particle size analyzer and transmission electron microscope.The drug loaded micelles could release drug continuously for more than 72 h,and laser irradiation could accelerate drug release.The drug loaded micelles irradiated by laser could enhance the anti-tumor effect in vitro,which IC 50 value was 14.81μg·mL^(-1),and its cytotoxicity increased to 1.43 folds compared with TF administrated only.Conclusion The micelles loaded with tegafur-pyropheophorbic acid A can release tegafur sustainable,and effectively improve the in vitro anti-tumor efficiency.