Blood nerve barrier permeability enables nerve targeting of circulating nanoparticles in experimental autoimmune neuritis

Guillain-Barré syndrome (GBS) is a devastating autoimmune disease of the peripheral nervous system (PNS) for which treatment options are strictly palliative. Several studies have shown attenuation of the well-characterized preclinical experimental autoimmune neuritis (EAN) model with systemically administered therapeutic compounds via a range of anti-inflammatory or immunomodulatory mechanisms. Despite this, clinical advancement of these findings is limited by dosing that is not translatable to humans or is associated with off-target and toxic effects. This is due, in part, to the blood-nerve barrier (BNB), which restricts access of the circulation to peripheral nerves. Here, we assessed the degree to which BNB permeability and immune cell infiltration over the course of EAN enable passive accumulation of circulating nanoparticles. We found that at stages of EAN defined by distinct clinical scores and pathology (onset, intermediate, peak), intravenously administered small molecules and nanoparticles ranging from 50–150 nm can permeate into the endoneurium from the endoneurial vasculature in a size- and disease stage-dependent manner. This permeation occurs uniformly in both sciatic nerves and in proximal and distal regions of the nerves. We propose that this passive targeting serves as a platform by which potential therapies for GBS can be reevaluated and investigated preclinically in nanoparticle delivery systems.