title: Delivery of large molecules via poly(butyl cyanoacrylate) nanoparticles into the injured rat brain.
abstract: Poly(n-butyl-2-cyanoacrylate) (PBCA) nanoparticles have been successfully applied to deliver small-molecule drugs to the central nervous system (CNS). However, it is unclear whether PBCA nanoparticles can be used as the delivery system for large molecules to potentially treat traumatic brain injury (TBI). In this study, we tested the capacity of PBCA nanoparticles in passing through the blood-brain barrier (BBB) and transporting large molecules into normal and injured brains in the rat. We first synthesized PBCA nanoparticles by dispersion polymerization and then loaded the particles with either horseradish peroxidase (HRP, 44 kDa) or enhanced green fluorescent protein (EGFP, 29 kDa), which were further coated with polysorbate 80. Next, the polysorbate 80-coated HRP or EGFP-loaded PBCA nanoparticles were intravenously injected into the normal and brain-injured rats. We found that, at 45 min after injection, PBCA nanoparticle-delivered HRP or EGFP was hardly detected in the normal brains of the rats, but a small amount of EGFP carried by PBCA nanoparticles was noted in the normal brains 48 h after administration, which was further confirmed by immunolocalization with anti-EGFP antibodies. In contrast, at 4 h after TBI with a circulation time of 45 min, although the penetration of HRP or EGFP alone was hampered by the BBB, the PBCA nanoparticle-delivered HRP or EGFP was widely distributed near injured sites. Together, our findings provide histological evidence that PBCA nanoparticles can be used as an efficient delivery system for large molecules to overcome the barrier in the brain with TBI.
authors.affiliation: Department of Neurological Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Pan
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Shi
authors.forename: Xianjian
authors.initials: X
authors.lastname: Huang
authors.forename: Nengqin
authors.initials: N
authors.lastname: Jia
authors.forename: Ji-Yao
authors.initials: JY
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000737:chemistry*; D001930:Brain Injuries / Q000378:metabolism*; D004058:Diffusion; D004659:Enbucrilate / Q000737:chemistry*; D008297:Male; D046912:Multiprotein Complexes / Q000737:chemistry*; D053769:Nanocapsules / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D046912:Multiprotein Complexes; D053769:Nanocapsules; D004659:Enbucrilate