基于β-环糊精的阿霉素纳米HBc-VLPs的制备与性能评价

Preparation and Performance Evaluation of Adriamycin Nano HBC-VLPs Based on β-Cyclodextrin

通过重组的乙肝核心蛋白病毒样颗粒(HBc-VLPs)对阿霉素进行包封已经被证实有良好的靶向缓释效果,但是载药量和稳定性方面仍待提升,本文基于β-环糊精(β-CD)建立一种有效的HBc-VLPs-β-CD-DOX制备方法,利用高效液相、粒径、透射电镜等方式评价HBc-VLPs-β-CD-DOX的表征、载药量、稳定性以及乳腺癌细胞的抗肿瘤活性。结果显示,HBc-VLPs-β-CD-DOX呈球形,粒径为(30±2)nm左右,大小形态均一,其载药量可达250μg/mL,相较于HBc-DOX-VLPs有明显提升,粒径结果显示HBc-VLPs-β-CD-DOX在4°C的环境下可存放30d,动态透析法显示HBc-VLPs-β-CD-DOX在生理状态下有较好的稳定性,DOX的泄漏率不到1%,细胞毒性结果显示,HBc-VLPs-β-CD-DOX对于4T1细胞的有较好的杀伤作用,IC50可达到1.128μg/mL。研究结果表明,HBc-VLPs-β-CD-DOX制备成功并建立了高效的包封方法,表现出良好的保存稳定性和生理稳定性以及对肿瘤细胞的杀伤效果,是一种非常有前景的纳米靶向药物。

The inclusion of adriamycin by hepatitis B core protein virus-like particles(HBc-VLPs) has been shown to have a good targeted and sustained release effect, but drug loadings and stability still need to improve, this article is based on β-cyclodextrin(β-CD) to establish an effective HBc-VLPs-β-CD-DOX preparation method, using the liquid phase, particle size, high tem methods such as evaluation of HBc-VLPs-β-CD-DOX characterization, drug-polymer interactions, stability, and the antitumor activity of breast cancer cells., according to the results of HBc-VLPs-β-CD-DOX spherical, particle size of(30 + 2) nm, uniform size form, the drug-polymer interactions can be up to 250 μg/mL, compared with HBc-VLPs-DOX has obvious improvement, particle size distribution results show HBc-VLPs-β-CD-DOX at 4°C for 30 days, the dynamic dialysis method show HBc-VLPs-β-CD-DOX have good stability, in a physiological manner of DOX leakage rate is less than 1%, cytotoxicity, according to the results of HBc-VLPs-β-CD-DOX had better killing effect on 4T1 cells with IC50up to 1.128 μg/mL.The results show that HBc-VLPs-β-CD-DOX has been successfully prepared and an efficient encapsulation method has been established, showing good preservation stability and physiological stability as well as killing effect on tumor cells, and it is a promising nano-targeted drug.