The blood-brain barrier (BBB) is an obstacle for clinicians and complicates the treatment of diseases of the central nervous system (CNS), which can require BBB-impermeable medicines, such as large-molecule neurotrophic factors. Although the BBB is disrupted after traumatic brain injury (TBI), the extent of the barrier opening may vary in different trauma conditions and may be changed with the development of TBI. Now, researchers from the Shanghai Jiao Tong University School of Medicine, China, are investigating the hypothesis that PBCA nanoparticles can efficiently deliver large molecules into the injured brain.
|PBCA nanoparticle-mediated delivery of large molecule EGFP into injured brain tissue.|
In a rat model of TBI, the team found that while the penetration of large-molecule horseradish peroxidase (HRP) alone was hampered by the disrupted barrier post trauma, large amounts of PBCA nanoparticle-delivered molecules could be distributed in the brain parenchyma through the BBB after TBI.
The ability of PBCA nanoparticles to transport material was further confirmed by another experiment, in which the large-molecule-enhanced green fluorescent protein (EGFP) carried by PBCA nanoparticles was found to be greatly distributed around the injured area (shown by an asterisk in the image) of the brain post trauma compared with EGFP alone (figures A and B).
These results imply that PBCA nanoparticles facilitate the penetration of the large molecules across the barrier post trauma. In contrast, under normal conditions, it took 48 hours for PBCA nanoparticles to deliver a small amount of EGFP into the brain compared with 45 min after TBI.
The findings demonstrate three points: first, the successful entry via nanoparticles is not due to the BBB opening after TBI because the disrupted barrier limited the penetration of the HRP and EGFP alone; second, the particle-mediated penetration time is much shorter in the injured brain than that in the normal brain, so patients may benefit from the rapid delivery; third, PBCA nanoparticles may contribute to the increase of the therapeutic efficacy of medicine in TBI therapy since the particles can deliver more of these large molecules into the injured brain compared with those in the normal rat brain.
Full details can be found in the journal Nanotechnology.
About the author
Yong Lin, MD, PhD in neurosurgery, performed this study. Yaohua Pan, MD, PhD, a neurosurgeon, and Xianjian Huang, a PhD student in the Department of Neurosurgery, Renji hospital, Shanghai Jiao Tong University School of Medicine, China, also contributed to the research work. Ji-yao Jiang, MD, PhD, a professor and chairman of the Neurosurgery Department, guided this work. Yinfeng Shi, a masters student at Shanghai Normal University, China, made the PBCA nanoparticles for this experiment. Nengqin Jia, PhD, a professor at Shanghai Normal University, gave advice on nanoparticle preparation.