Apo E-Functionalization of Solid Lipid Nanoparticles Enhances Brain Drug Delivery: Uptake Mechanism and Transport Pathways.
Ana Rute NevesJoana Fontes QueirozSofia A Costa LimaSalette ReisPublished in: Bioconjugate chemistry (2017)
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.
Keyphrases
- drug delivery
- resting state
- white matter
- flow cytometry
- functional connectivity
- cerebral ischemia
- cognitive decline
- quantum dots
- multiple sclerosis
- type diabetes
- stem cells
- deep learning
- photodynamic therapy
- electronic health record
- drug release
- early stage
- lymph node
- artificial intelligence
- machine learning
- mild cognitive impairment
- blood brain barrier
- rectal cancer