Apo E-Functionalization of Solid Lipid Nanoparticles Enhances Brain Drug Delivery: Uptake Mechanism and Transport Pathways

Bioconjug Chem. 2017 Apr 19;28(4):995-1004. doi: 10.1021/acs.bioconjchem.6b00705. Epub 2017 Apr 5.

Abstract

Several strategies have been implemented to enhance brain drug delivery, and herein solid lipid nanoparticles functionalized with apolipoprotein E were tested in hCMEC/D3 cell monolayers. The mean diameter of 160 nm, negative charge of -12 mV, and their lipophilic characteristics make these nanosystems suitable for brain delivery. Confocal images and flow cytometry data showed a cellular uptake increase of 1.8-fold for SLN-Palmitate-ApoE and 1.9-fold for SLN-DSPE-ApoE when compared with the non-functionalized SLNs. Clathrin-mediated endocytosis was distinguished as the preferential internalization pathway involved in cellular uptake and nanoparticles could cross the blood-brain barrier predominantly by a transcellular pathway. The understanding of the mechanisms involved in the transport of these nanosystems through the blood-brain barrier may potentiate their application on brain drug delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins E / metabolism*
  • Blood-Brain Barrier / metabolism*
  • Brain / metabolism
  • Cell Line
  • Drug Carriers / metabolism*
  • Drug Delivery Systems
  • Humans
  • Lipid Metabolism
  • Lipids / chemistry
  • Nanoparticles / metabolism*
  • Palmitates / metabolism
  • Phosphatidylethanolamines / metabolism

Substances

  • Apolipoproteins E
  • Drug Carriers
  • Lipids
  • Palmitates
  • Phosphatidylethanolamines
  • 1,2-distearoylphosphatidylethanolamine