包载表柔比星的生物素化泊洛沙姆聚合物胶束的构建与体内外初步评价  

Construction and in vitro and in vivo Preliminary Evaluation of Biotin-poloxamer Conjugate Polymeric Micelles for Epirubicin

作　　者：林晓晓[1] 林光勇[1] 林正锋[1] 

机构地区：[1]温州医科大学附属第二医院,浙江温州325027

出　　处：《中国药师》2018年第2期241-245,共5页China Pharmacist

摘　　要：目的:把生物素接枝到泊洛沙姆上制备包载表柔比星(EPI)的生物素-泊洛沙姆(BP)胶束。方法:分别对包载EPI的BP胶束的粒径、Zeta电位、表面形态、载药量、包封率及药物释放等方面进行考察和表征。用骨髓白血病HL-60细胞株评估包载EPI的BP胶束的体外细胞毒性。裸鼠皮下注射HL-60细胞建立肿瘤模型,考察包载EPI的BP胶束抑制肿瘤的影响。结果:这些纳米粒子的尺寸约为100 nm。荧光显微镜观察得出生物素结合的胶束有助于细胞摄取。抑制肿瘤体积增长的顺序:包载EPI的BP胶束>包载EPI的单胺封端的泊洛沙姆(MATP)胶束>包载EPI的泊洛沙姆胶束>单纯EPI。结论:与非靶向胶束相比,BP胶束表现出显著的的抗肿瘤活性和低毒性。拥有增强通透性和滞留性(EPR)效应和肿瘤靶向两大优势,BP胶束可能发展成为一个新的运载化疗药物的途径。尚需进一步进行其他细胞实验和大动物实验证明该肿瘤靶向技术。Objective： To prepare biotin-poloxamer（ BP） conjugate micelles for epirubicin through biotin conjugated on poloxamer. Methods： Epirubicin（ EPI） was encapsulated in BP micelles. The EPI-loaded BP micelles were characterized by its particle size,zeta potential,surface morphology,as well as the efficiency of drug loading and drug encapsulation and drug release. Marrow leukemia HL-60 cells were used to evaluate the cell cytotoxicity of EPI-loaded BP micelles in vitro. The tumor model in nude mice was established through the subcutaneous injection of HL-60 cells,and then the inhibitory effect of EPI-loaded BP micelles on tumor volume growth was investigated. Results： It was found that the average particle size of EPI-loaded BP micelles was about 100 nm. In addition,the enhanced cellular uptake ability of EPI-loaded BP micelles was proved by fluorescence microscope observation. The efficiency order of the tumor volume growth inhibition was： EPI-loaded BP micelles EPI-loaded MATP micelles EPI-loaded poloxamer micelles EPI. BP micelles showed significant antitumor activity and low toxicity when compared with the non-targeted micelles. Conclusion：With the advantages of EPR effect and tumor-targeting potential,BP conjugate micelles might be developed as a new system for chemotherapeutics. However,the tumor targeting technique should be demonstrated further by the other cell experiments and large animal experiments.

关 键 词：生物素-泊洛沙姆共轭物 表柔比星 胶束 

分 类 号：R944.9[医药卫生—药剂学]