Abstract
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.
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