title: Effect of PLGA NP size on efficiency to target traumatic brain injury.
abstract: Necrotic cell death occurs exclusively under pathological conditions, such as ischemic diseases. Necrosis imaging is of diagnostic value and enables early measurement of treatment efficiency in ischemic patients. Here we explored the targeted delivery of particles, with diameters of approximately 100nm, 200nm and 800nm, consisting of a poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) core coated with a polyethylene glycol-lipid (PEG) layer. Targeted delivery was facilitated by coupling the amino end group of the polyethylene glycol-layer to 800CW imaging agent, which specifically binds to intracellular proteins of cells that have lost membrane integrity, thus revealing the extent of the damaged area. We found that smaller NPs (100nm), with an appropriate coating, diffuse throughout the traumatic brain injury (TBI) in mice. Optical imaging revealed that smaller (100-nm) PEG-coated NPs carrying 800CW penetrated deeper into the mouse brain than large 800CW containing NPs (800nm). The importance of the 800CW as a ligand to target the necrotic tissue was further confirmed in living mice. The ability to achieve brain penetration with smaller NPs is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find application in the treatment of stroke, brain tumors, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible.
authors.affiliation: Nanomedicine and Molecular Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands. Electronic address: l.j.cruz_ricondo@lumc.nl.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Cruz
authors.affiliation: Percuros, Enschede, The Netherlands.
authors.forename: Marieke A
authors.initials: MA
authors.lastname: Stammes
authors.affiliation: Nanomedicine and Molecular Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
authors.forename: Ivo
authors.initials: I
authors.lastname: Que
authors.affiliation: Percuros, Enschede, The Netherlands.
authors.forename: Ermond R
authors.initials: ER
authors.lastname: van Beek
authors.affiliation: Nanomedicine and Molecular Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
authors.forename: Vicky T
authors.initials: VT
authors.lastname: Knol-Blankevoort
authors.affiliation: Nanomedicine and Molecular Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
authors.forename: Thomas J A
authors.initials: TJA
authors.lastname: Snoeks
authors.affiliation: Percuros, Enschede, The Netherlands.
authors.forename: Alan
authors.initials: A
authors.lastname: Chan
authors.affiliation: Nanomedicine and Molecular Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Kaijzel
authors.affiliation: Nanomedicine and Molecular Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands. Electronic address: C.W.G.M.Lowik@lumc.nl.
authors.forename: Clemens W G M
authors.initials: CWGM
authors.lastname: Löwik
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014018:Tissue Distribution
chemical_list: D001557:Benzenesulfonates; D004337:Drug Carriers; D005456:Fluorescent Dyes; C562366:IRDye 800CW; D007211:Indoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Brain injury; Contrast agents; Imaging; Nanoparticles; PLGA; Targeting