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Size-Selective Transfer of Lipid Nanoparticle-Based Drug Carriers Across the Blood Brain Barrier Via Vascular Occlusions Following Traumatic Brain Injury. | LitMetric

AI Article Synopsis

  • The study explores how lipid nano-emulsion droplets (LNDs) of two sizes (30 nm and 80 nm) travel through the blood-brain barrier (BBB) in mouse models after traumatic brain injury (TBI).
  • Using advanced imaging techniques, researchers found that after TBI, 30 nm LNDs can exit the blood vessels and reach brain cells, while 80 nm LNDs remain inside the blood vessels.
  • The results indicate that certain occlusions in the brain's blood vessels act as "gates," allowing smaller nanocarriers to penetrate the BBB, highlighting the potential for targeted drug delivery systems in brain injuries.

Article Abstract

The current lack of understanding about how nanocarriers cross the blood-brain barrier (BBB) in the healthy and injured brain is hindering the clinical translation of nanoscale brain-targeted drug-delivery systems. Here, the bio-distribution of lipid nano-emulsion droplets (LNDs) of two sizes (30 and 80 nm) in the mouse brain after traumatic brain injury (TBI) is investigated. The highly fluorescent LNDs are prepared by loading them with octadecyl rhodamine B and a bulky hydrophobic counter-ion, tetraphenylborate. Using in vivo two-photon and confocal imaging, the circulation kinetics and bio-distribution of LNDs in the healthy and injured mouse brain are studied. It is found that after TBI, LNDs of both sizes accumulate at vascular occlusions, where specifically 30 nm LNDs extravasate into the brain parenchyma and reach neurons. The vascular occlusions are not associated with bleedings, but instead are surrounded by processes of activated microglia, suggesting a specific opening of the BBB. Finally, correlative light-electron microscopy reveals 30 nm LNDs in endothelial vesicles, while 80 nm particles remain in the vessel lumen, indicating size-selective vesicular transport across the BBB via vascular occlusions. The data suggest that microvascular occlusions serve as "gates" for the transport of nanocarriers across the BBB.

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Source
http://dx.doi.org/10.1002/smll.202200302DOI Listing

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