title: Brain-targeted delivery of resveratrol using solid lipid nanoparticles functionalized with apolipoprotein E.
abstract: BACKGROUND
  The present study takes advantage of the beneficial effects of resveratrol as a neuroprotective compound. Resveratrol-loaded solid lipid nanoparticles were functionalized with apolipoprotein E which can be recognized by the LDL receptors overexpressed on the blood-brain barrier.
  
  
  RESULTS
  Transmission electron microscopy images revealed spherical nanoparticles, dynamic light scattering gave a Z-average lower than 200 nm, and a zeta potential of around -13 mV and very high resveratrol entrapment efficiency (ca. 90 %). In vitro cytotoxic effects were assessed by MTT and LDH assays in hCMEC/D3 cell line and revealed no toxicity up to 50 μM over 4 h of incubation. The permeability through hCMEC/D3 monolayers showed a significant increase (1.8-fold higher) for resveratrol-loaded solid lipid nanoparticles functionalized with apolipoprotein E when compared to non-functionalized ones.
  
  
  CONCLUSIONS
  In conclusion, these nanosystems might be a promising strategy for resveratrol delivery into the brain, while protecting it from degradation in the blood stream. Graphical abstract .
authors.affiliation: UCIBIO/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
authors.forename: Ana Rute
authors.initials: AR
authors.lastname: Neves
authors.affiliation: UCIBIO/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.
authors.forename: Joana Fontes
authors.initials: JF
authors.lastname: Queiroz
authors.affiliation: UCIBIO/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. shreis@ff.up.pt.
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D001053:Apolipoproteins / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008055:Lipids / Q000008:administration & dosage*; D053758:Nanoparticles / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010316:Particle Size; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D001053:Apolipoproteins; D004337:Drug Carriers; D008055:Lipids; D018696:Neuroprotective Agents; D013267:Stilbenes; D000077185:Resveratrol
keywords: Apolipoprotein E; Blood–brain barrier; Brain delivery; Resveratrol; Solid lipid nanoparticles