叶酸介导阿霉素白蛋白纳米粒的制备及细胞学研究

Preparation and Cytology of Folic Acid-Albumin Nanoparticles Loaded with Doxorubicin

以牛血清白蛋白为载体材料,制备叶酸介导的具有主动抗肿瘤靶向功能的新型高载药量的阿霉素白蛋白纳米粒,并对其进行体外抗肿瘤活性研究.采用去溶剂化法制备白蛋白纳米粒,再利用白蛋白表面上的活性氨基与叶酸活性酯反应得到具有主动靶向叶酸介导的阿霉素白蛋白纳米粒,对其性质进行考察.以市售阿霉素粉针剂为对照,采用MTT法,考察主动靶向制剂对人肝癌细胞HEPG2和人胃癌细胞SGC7901的体外抗肿瘤活性.制备出叶酸介导的载阿霉素白蛋白纳米粒,其粒径大小平均为(137.43±0.67)nm,粒度分布较为均匀.包封率为(89.43±0.67)%,载药量高达(19.03±0.32)%.体外释放实验表明:叶酸介导阿霉素白蛋白纳米粒具有缓释性质,24 h内药物释放率约为26.7%.体外药效学结果显示:FA-BSANPs/DOX和DOX对高表达的人肝癌细胞HEPG2细胞的IC 50值分别为4.98μmol/L和5.13μmol/L,对人胃癌细胞SGC7901的IC 50值分别为4.85μmol/L和5.02μmol/L.以白蛋白为载体、偶联叶酸可制备阿霉素高载药量白蛋白纳米粒,其在体外对HEPG2细胞和SGC7901具有杀伤作用.与盐酸阿霉素粉针剂相比,显示出较强的肿瘤细胞抑制效果.

Folic acid-mediated doxorubicin alburmin nanoparticles with active anti-tumor targeting function were prepared using bovine serum albumin as carrier material,and their anti-tumor activity in vitro was studied.FA-BSANPs/DOX with active anti-tumor adriamycin were obtained by the amino group of albumin nanoparticles of desolvation and the folic acid active ester.And the properities of FA-BSANPs/DOX were investigated.MTT method was applied to determine the in vitro anticancer activity of FA-BSANPs/DOX in HEPG2 and SGC7901 compared with DOX.FA-BSANPs/DOX was successfully formulated.The average particle size of FA-BSANPs/DOX was(137.43±0.67)nm with uniform particle size distribution.The entrap meet efficiency was(89.43±0.67)%and the drug loading rate reached at(19.03±0.32)%.The result of the in vitro release of FA-BSANPs/DOX exhibited that cumulative release amount 24 h was 26.7%indicating that FA-BSANPs/DOX had the good quality of slow releasing.The pharmacodynamics in vitro experiment results revealed that the values of FA-BSANPs/DOX and DOX in HEPG2 were 4.98μmol/L and 5.13μmol/L,in SGC7901 were 4.85μmol/L and 5.02μmol/L,respectively.Albumin as carrier material can prepare the high drug-loading albumin nanoparticles.FA-BSANPs/DOX are more effective in killing HEPG2 and SGC7901 in vitro.It showed strong inhibitory effect on tumor cells,which may be hope to be a kind of potential preparation of albumin nanoparticles.