内皮细胞靶向性氟尿嘧啶脂质微泡的制备及稳定性研究  

Preparation and Stability of a New Type of Endothelial Cell Targeting Lipid Microbubbles Loaded with 5-Fluorouracil

作　　者：张悦 孙可欣 顾东岳 李穆琼 兰婷 何光彬 刘丽文 文爱东 Zhang Yue;Sun Kexin;Gu Dongyue;Li Muqiong;Lan Ting;He Guangbin;Liu Liwen;Wen Aidong(Department of Ultrasound,Xijing Hospital,Air Force Military Medical University,Xi'an 710032,China;School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University;Department of Pharmacy,Xijing Hospital,Air Force Military Medical University;Department of Pharmacology,Air Force Military Medical University)

机构地区：[1]空军军医大学第一附属医院超声医学科,西安710032 [2]中国药科大学基础医学与临床药学院 [3]空军军医大学第一附属医院药剂科 [4]空军军医大学药学系

出　　处：《中国药师》2021年第6期1051-1056,共6页China Pharmacist

基　　金：陕西省统筹创新工程创新项目(编号:2015KTCL03-11)。

摘　　要：目的:制备载氟尿嘧啶(5-Fu)的新型内皮细胞靶向脂质微泡(5-Fu-LF9-MBs),对其合成、制备及体外稳定性进行研究,探索其作为一种新型内皮细胞靶向药物载体的可行性。方法:合成以Dll4-Notch通路特异性相关的结构域的活性片段LF9,进一步包载抗癌药5-Fu,制得载药脂质微泡5-Fu-LF9-MBs。以粒径、Zeta电位、包封率(EE)、载药量(DL)、PDI等评价指标筛选出脂质微泡最佳制备处方,并通过荧光显微镜考察5-Fu-MBs和5-Fu-LF9-MBs两种脂质微泡的形态和其在不同浓度浓度BSA溶液中的稳定性。结果:靶向脂质微泡(5-Fu-LF9-MBs)能高效负载5-Fu,包封率为86.9%,载药量为0.05%,且体外稳定性佳。结论:LF9修饰的新型脂质微泡能够高效负载5-Fu,有一定的临床应用潜力。Objective:To prepare a new type of endothelial cell targeting lipid microbubbles loaded with fluorouracil(5-Fu-LF9-MBs),and to study the synthesis,preparation and stability in vitro of the lipid microbubbles to explore its feasibility as a new endothelial cell targeting drug carrier.Methods:The active fragment LF9 was synthesized from the domain specifically related to the Dll4-notch pathway,and fluorouracil loaded microbubbles were prepared.Formulation optimization of 5-Fu-LF9-MBs was accomplished using particle size,Zeta potential,entrapment efficiency(EE),PDI and drug loading(DL)as the evaluation indexes.The morphology of 5-Fu-MBs and 5-Fu-LF9-MBs were observed under a fluorescence microscope,and their stability in BSA solution with different concentrations was investigated.Results:The targeting 5-Fu-LF9-MBs were able to load 5-fluorouracil efficiently.The EE and DL of microbubbles was 86.9% and 0.05%,respectively,and the results of the stability test verified good stability in vitro.Conclusion:Novel peptide LF9 modified lipid microbubbles can load fluorouracil efficiently,and have certain clinical application potential.

关 键 词：氟尿嘧啶 靶向治疗 脂质微泡 稳定性 

分 类 号：R944.9[医药卫生—药剂学]