title: Traumatic brain injury opens blood-brain barrier to stealth liposomes via an enhanced permeability and retention (EPR)-like effect.
abstract: The opening of the tight junctions in the blood-brain barrier (BBB) following traumatic brain injury (TBI) is hypothesized to be sufficient to enable accumulation of large drug carriers, such as stealth liposomes, in a similar manner to the extravasation seen in tumor tissue via the enhanced permeability and retention (EPR) effect. The controlled cortical impact model of TBI was used to evaluate liposome accumulation in mice. Dual-radiolabeled PEGylated liposomes were administered either immediately after induction of TBI or at increasing times post-TBI to mimic the likely clinical scenario. The accumulation of radiolabel in the brain tissue ipsilateral and contralateral to the site of trauma, as well as in other organs, was evaluated. Selective influx of liposomes occurred at 0-8 h after injury, while the barrier closed between 8 and 24 hr after injury, consistent with reports on albumin infiltration. Significantly enhanced accumulation of liposomes occurred in mice subjected to TBI compared to anaesthetized controls, and accumulation was greater in the injured versus the contralateral side of the brain. Thus, stealth liposomes show potential to enhance drug delivery to the site of brain injury with a wide range of encapsulated therapeutic candidates.
authors.affiliation: a Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville , VIC , Australia .|b ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville , VIC , Australia .
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
authors.affiliation: c Australian Centre for Blood Diseases, Monash University Alfred Hospital , Melbourne , VIC , Australia .|d Molecular Neurotrauma and Haemostasis, Central Clinical School , Monash University , VIC , Australia .
authors.forename: Adam
authors.initials: A
authors.lastname: Galle
authors.affiliation: c Australian Centre for Blood Diseases, Monash University Alfred Hospital , Melbourne , VIC , Australia .|d Molecular Neurotrauma and Haemostasis, Central Clinical School , Monash University , VIC , Australia .
authors.forename: Maria
authors.initials: M
authors.lastname: Daglas
authors.affiliation: e Department of Surgery , Monash University Alfred Hospital , Melbourne , VIC , Australia .|f F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences , Bethesda , MD , USA , and.|g Monash Institute of Medical Engineering, Monash University , Melbourne , VIC , Australia.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Rosenfeld
authors.affiliation: c Australian Centre for Blood Diseases, Monash University Alfred Hospital , Melbourne , VIC , Australia .|d Molecular Neurotrauma and Haemostasis, Central Clinical School , Monash University , VIC , Australia .
authors.forename: Robert
authors.initials: R
authors.lastname: Medcalf
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D010316:Particle Size; D010539:Permeability; D011877:Radionuclide Imaging; D019108:Tight Junctions / Q000473:pathology; D014316:Tritium / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; D008081:Liposomes; D014316:Tritium
keywords: Albumin; blood–brain barrier; extravasation; stealth liposomes; traumatic brain injury