Open Access

Patrick Bechinger, Lucas Ezequiel Serrano Sponton, Daniela Eldahaby, Daniel Stephan Jussen, Harald Krenzlin, Verena Grützner, Nicole Riede, Anna Musyanovich, Malte Ottenhausen, Florian Alexander Ringel, Beat Alessandri

• Background: A growing interest exists in using polymeric nanoparticles (NPs) especially functionalized with surface-active substances as carriers across the blood brain barrier (BBB) for potentially effective drugs in traumatic brain injury (TBI). However, the organ distribution of intravenous administrated biodegradable and non-biodegradable NPs coated with different surfactants, how much of the administrated dose reach the brain parenchyma in areas with intact and opened BBB after trauma, as well as whether they elicit an inflammatory response is still to be clarified. Methods: The organ distribution, brain penetration and eventual inflammatory activation of polysorbate-80 (Tw80) and sodium-lauryl-sulfate (SDS) coated poly l-lactide (PLLA) and perfluorodecyl acrylate (PFDL) nanoparticles were evaluated after intravenous administration in rats prior and after undergoing controlled cortical impact (CCI). Results: A significant highest NP uptake at 4 and 24 hs was observed in the liver and spleen, followed by the brain and kidney, with minimal concentrations in the lungs and heart for all NPs. After CCI, a significant increase of NP uptake at 4 hs and 24 hs was observed within the traumatized hemisphere, especially in the perilesional area, although NPs were still found in areas away from CCI and the contralateral hemisphere in similar concentrations as in non-CCI subject. NPs were localized in neurons, glial and endovascular cells. Immunohistochemical staining against GFAP, Iba1, TNFα and IL1β demonstrated no glial activation or neuroinflamatory changes. Conclusions: Tw80 and SDS coated biodegradable (PLLA) and non-biodegradrable (PFDL) NPs reach the brain parenchyma in both areas of traumatized and undamaged brain with disrupted and intact BBB, even though a high amount of them are retained in the liver and the spleen. No inflammatory reaction is elicited by these NPs within 24 hs after application. These preliminary promising results postulate the effectiveness and safety of these NPs as drug-carriers for the treatment of TBI.