A1 Refereed original research article in a scientific journal
Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier
Authors: Habib Baghirov, Didem Karaman, Tapani Viitala, Alain Duchanoy, Yan-Ru Lou, Veronika Mamaeva, Evgeny Pryazhnikov, Leonard Khiroug, Catharina de Lange Davies, Cecilia Sahlgren, Jessica M. Rosenholm
Publisher: PUBLIC LIBRARY SCIENCE
Publication year: 2016
Journal: PLoS ONE
Journal name in source: PLOS ONE
Journal acronym: PLOS ONE
Article number: ARTN e0160705
Volume: 11
Issue: 8
Number of pages: 22
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0160705
Drug delivery into the brain is impeded by the blood-brain-barrier (BBB) that filters out the vast majority of drugs after systemic administration. In this work, we assessed the transport, uptake and cytotoxicity of promising drug nanocarriers, mesoporous silica nanoparticles (MSNs), in in vitro models of the BBB. RBE4 rat brain endothelial cells and Madin-Darby canine kidney epithelial cells, strain II, were used as BBB models. We studied spherical and rod-shaped MSNs with the following modifications: bare MSNs and MSNs coated with a poly (ethylene glycol)-poly(ethylene imine) (PEG-PEI) block copolymer. In transport studies, MSNs showed low permeability, whereas the results of the cellular uptake studies suggest robust uptake of PEG-PEI-coated MSNs. None of the MSNs showed significant toxic effects in the cell viability studies. While the shape effect was detectable but small, especially in the real-time surface plasmon resonance measurements, coating with PEG-PEI copolymers clearly facilitated the uptake of MSNs. Finally, we evaluated the in vivo detectability of one of the best candidates, i.e. the copolymer-coated rod-shaped MSNs, by two-photon in vivo imaging in the brain vasculature. The particles were clearly detectable after intravenous injection and caused no damage to the BBB. Thus, when properly designed, the uptake of MSNs could potentially be utilized for the delivery of drugs into the brain via transcellular transport.
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