Tian Yong, Li Jian-Chun, Zhu Jin-Xiu, Zhu Na, Zhang Hong-Min, Liang Lili, Sun Lingyi
School of Pharmacy, Bengbu Medical College, Bengbu, Anhui, China (mainland).
Molecular Imaging Lab, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Med Sci Monit. 2017 May 22;23:2426-2435. doi: 10.12659/msm.904683.
BACKGROUND The aim of this study was to develop a novel Poloxamer-based drug delivery system featuring a tumor-targeting folate moiety, which was expected to provide better targeting properties and therapeutic effects compared with the traditional cubosomes (Cubs). MATERIAL AND METHODS Both folate-modified Cubs containing etoposide (ETP-Cubs-FA) and normal cubic nanoparticles loaded with etoposide (ETP-Cubs) were prepared through the fragmentation of bulk gels under the homogenization condition of 1500 bar, and a mean particle size of around 180 nm was obtained with a narrow size distribution. The cubosomes were further characterized by differential scanning calorimetry (DSC) and Polarized light microscopy (PLM). The release of ETP in vitro from these nanoparticles was found to be 82.5% at 36 h, showing a sustained release property compared with the free drug administration. RESULTS Folate-modified cubosomes exhibited best anti-proliferative activity followed by normal cubosomes and the free drug. A further cell uptake study of Rhodamine B-loaded Cubs-FA (Rh-B-Cubs-FA) showed a marked increase of cellular accumulation compared with free Rh-B and Rh-B-loaded Cubs (Rh-B-Cubs). In vivo Rh-B-based tumor imaging demonstrated that Cubs-FA specifically targeted the tumor tissue. CONCLUSIONS The folate-modified cubosomes containing ETP may be a promising drug candidate for antitumor treatment.
背景 本研究的目的是开发一种基于泊洛沙姆的新型药物递送系统，其具有肿瘤靶向叶酸部分，与传统立方液晶纳米粒（Cubs）相比，有望提供更好的靶向性能和治疗效果。材料与方法 通过在1500巴的均质条件下使块状凝胶破碎，制备了含有依托泊苷的叶酸修饰立方液晶纳米粒（ETP-Cubs-FA）和负载依托泊苷的普通立方纳米粒（ETP-Cubs），获得了平均粒径约为180nm且粒径分布窄的纳米粒。通过差示扫描量热法（DSC）和偏光显微镜（PLM）对立方液晶纳米粒进行了进一步表征。发现这些纳米粒中ETP在36小时时的体外释放率为82.5%，与游离药物给药相比具有缓释特性。结果 叶酸修饰的立方液晶纳米粒表现出最佳的抗增殖活性，其次是普通立方液晶纳米粒和游离药物。对负载罗丹明B的立方液晶纳米粒-FA（Rh-B-Cubs-FA）的进一步细胞摄取研究表明，与游离Rh-B和负载罗丹明B的立方液晶纳米粒（Rh-B-Cubs）相比，细胞内积累显著增加。基于体内Rh-B的肿瘤成像表明，立方液晶纳米粒-FA特异性靶向肿瘤组织。结论 含有ETP的叶酸修饰立方液晶纳米粒可能是一种有前途的抗肿瘤治疗候选药物。
