Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, 62102, Taiwan.
Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, 62102, Taiwan.
Int J Pharm. 2014 Apr 25;465(1-2):132-42. doi: 10.1016/j.ijpharm.2014.02.008. Epub 2014 Feb 10.
Brain-targeted delivery of etoposide (ETP) is important for treating malignant tumors in the central nervous system. This study presents the transport of ETP across the blood-brain barrier (BBB) using catanionic solid lipid nanoparticles (CASLNs) grafted with 5-HT-moduline. ETP-encapsulated CASLNs (ETP-CASLNs) were prepared in catanionic microemulsion and constructed into solid colloids by rapid cooling. In addition, the uptake of 5-HT-moduline-grafted ETP-CASLNs (5-HT-moduline/ETP-CASLNs) by human brain-microvascular endothelial cells (HBMECs) was visualized by immunochemical staining. We found that a maximal entrapment efficiency of ETP occurred at 0.75 mM of catanionic surfactants. An increase in the concentration of catanionic surfactants reduced the viability of HBMECs. Moreover, an increase in the concentration of 5-HT-moduline reduced the grafting efficiency of 5-HT-moduline, cell viability, and transendothelial electrical resistance of HBMEC monolayer, and enhanced the permeability of propidium iodide and ETP across the BBB. Surface-modified 5-HT-moduline/ETP-CASLNs can be promising drug delivery carriers for anti-brain tumor chemotherapy in preclinical trial.
脑靶向递送达泊苷（ETP）对于治疗中枢神经系统的恶性肿瘤非常重要。本研究使用与 5-HT-修饰素缀合的反离子固体脂质纳米粒（CASLNs）来研究 ETP 穿过血脑屏障（BBB）的转运。ETP 包封的 CASLNs（ETP-CASLNs）在反离子微乳液中制备，并通过快速冷却构建成固体胶体。此外，通过免疫化学染色可视化了 5-HT-修饰素/ ETP-CASLNs（5-HT-修饰素/ ETP-CASLNs）对人脑血管内皮细胞（HBMECs）的摄取。我们发现，ETP 的最大包封效率出现在 0.75 mM 的反离子表面活性剂时。反离子表面活性剂浓度的增加降低了 HBMECs 的活力。此外，5-HT-修饰素浓度的增加降低了 5-HT-修饰素的接枝效率、HBMEC 单层的细胞活力和跨内皮电阻，并增强了碘化丙啶和 ETP 穿过 BBB 的通透性。表面修饰的 5-HT-修饰素/ ETP-CASLNs 可能是临床前试验中抗脑肿瘤化疗的有前途的药物递送载体。
