title: Delivering etoposide to the brain using catanionic solid lipid nanoparticles with surface 5-HT-moduline.
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.
authors: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, 62102, Taiwan. Electronic address: chmyck@ccu.edu.tw.
authors: Yung-Chih
authors: YC
authors: Kuo
authors: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, 62102, Taiwan.
authors: Tsu-Yu
authors: TY
authors: Hong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D002412:Cations; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D017097:Electric Impedance; D042783:Endothelial Cells / Q000378:metabolism*; D005047:Etoposide / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles; D036103:Nanotechnology; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D010316:Particle Size; D013501:Surface-Active Agents / Q000737:chemistry / Q000633:toxicity; D013678:Technology, Pharmaceutical / Q000379:methods; D019108:Tight Junctions / Q000378:metabolism
chemical_list: C102005:5-HT-moduline; D000972:Antineoplastic Agents, Phytogenic; D002412:Cations; D004337:Drug Carriers; D008055:Lipids; D009479:Neuropeptides; D009842:Oligopeptides; D013501:Surface-Active Agents; D005047:Etoposide
keywords: 5-HT-moduline; Blood–brain barrier; Catanionic surfactant; Endothelium; Etoposide; Solid lipid nanoparticle