组氨酸修饰pH敏感PAMAM-His/DOX复合物的制备及体外评价  

Preparation and in vitro evaluation of histidine modified pH-sensitive PAMAM-His/DOX complexes

作　　者：宿露[1] 程丽芳[1] 程亮[1] 胡青[1] 杨佳[1] 陈大为[1,2] 

机构地区：[1]苏州大学药学院,苏州215123 [2]沈阳药科大学,沈阳110016

出　　处：《中国新药杂志》2016年第4期459-463,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金青年基金(81302719);国家自然科学基金面上项目(81173004)

摘　　要：目的:构建组氨酸(His)修饰pH敏感响应的载抗肿瘤药物阿霉素(DOX)复合物PAMAM-His/DOX,并对其进行表征及初步评价。方法:通过控制His和PAMAM的投料比,合成3种不同His修饰程度的PAMAM-His载体;采用物理包埋的方式将DOX包载在PAMAM的疏水空腔内制备系列载药复合物。对各载药复合物的粒径、电位、包封率、载药量、体外释放行为等进行考察,并采用MTT法评价各复合物对乳腺癌细胞MCF-7的细胞毒性作用。结果:PAMAM-His/DOX复合物的粒径均在10nm左右;随着His修饰程度的增加,其Zeta电位降低,且对抗MCF-7的细胞毒性增加;体外释放实验结果表明复合物具有明显的pH酸敏感特性,并且在酸性条件下(pH5.0),药物累积释放量与His修饰程度成正比。结论:本实验成功制备并初步评价了3种His修饰程度的PAMAM-His/DOX,为下一步的体内外抗肿瘤研究奠定了理论基础。Objective： To construct and evaluate the histidine modified pH-sensitive DOX-loaded complexes PAMAM-His/DOX, based on polyamidoamine dendrimer （PAMAM）. Methods： By controlling the feed ratio of the histidine （His） and PAMAM, the His-modified PAMAM （PAMAM-His） with three different modification degrees were successfully synthesized. Then, doxorubicin （DOX） was loaded into the hydrophobic cavity of PAM- AM-His via physical encapsulation to obtain PAMAM-His/DOX complexes. The particle size, Zeta potential, encapsulation efficiency, drug loading and in vitro release profiles of each conjugate were investigated. The cytotoxicity against breast cancer cells （MCF-7） was also evaluated by MTT assay. Results： All the particle sizes of PAM- AM-His/DOX complexes were about 10 nm, and the Zeta potential was decreased with the His modification degree increased, while the cytotoxicity against MCF-7 increased. The in vitro release results showed that the complexes had a pH-sensitive property, especially in pH 5.0 buffer. Cumulative release amount of DOX was proportional to the degree of His modification. Conclusion： Three PAMAM-His/DOX complexes have been successfully constructed and preliminarily evaluated, providing a basis for the further anti-tumor experiments in vivo and in vitro.

关 键 词：组氨酸 PAMAM 阿霉素 PH敏感性 体外评价 

分 类 号：R943.42[医药卫生—药剂学]