Abstract
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.
Highlights
The blood-brain barrier (BBB) is the most extensive of barriers that protect the brain’s internal milieu and maintain its homeostasis [1]
The synthesis parameters were varied in order to investigate the effect of aspect ratio, where rod-shaped mesoporous silica nanoparticles (MSNs) have previously been observed to be more efficiently internalized by cells [7, 15, 16]
The morphology and mesostructure of the obtained pure spherical MSN and rod-shaped MSNs were investigated with electron microscopy (EM), as shown in Fig 2 below
Summary
The blood-brain barrier (BBB) is the most extensive of barriers that protect the brain’s internal milieu and maintain its homeostasis [1]. The BBB is formed by brain capillary. Mesoporous Silica Nanoparticle Transport across the Blood-Brain Barrier provided support in the form of salaries for authors EP and LK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section
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