title: Toxicity of polymeric nanoparticles in vivo and in vitro.
abstract: Polybutylcyanoacrylate nanoparticles (PBCA NPs) are candidates for a drug delivery system, which can cross the blood-brain barrier (BBB). Because little is known about their toxicity, we exposed cells to PBCA NPs in vitro and in vivo and monitored their life and death assays. PBCA NPs were fabricated with different surfactants according to the mini-emulsion technique. Viabilities of HeLa and HEK293 cells after NP incubation were quantified by analysing cellular metabolic activity (MTT-test). We then repetitively injected i.v. rhodamine-labelled PBCA NP variations into rats and monitored the survival and morphology of retrogradely labelled neurons by in vivo confocal neuroimaging (ICON) for five weeks. To test for carrier-efficacy and safety, PBCA NPs loaded with Kyotorphin were injected in rats, and a hot plate test was used to quantify analgesic effects. In vitro, we found dose-dependent cell death which was, however, only detectable at very high doses and mainly seen in the cultures incubated with NPs fabricated with the tensids SDS and Tween. However, the in vivo experiments did not show any NP-induced neuronal death, even with particles which were toxic at high dose in vitro, i.e. NPs with Tween and SDS. The increased pain threshold at the hot plate test demonstrated that PBCA NPs are able to cross the BBB and thus comprise a useful tool for drug delivery into the central nervous system (CNS). Our findings showing that different nanoparticle formulations are non-toxic have important implications for the value of NP engineering approaches in medicine.
authors.affiliation: Institute of Medical Psychology, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Voigt
authors.affiliation: Institute of Medical Psychology, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Henrich-Noack
authors.affiliation: Institute of Process Engineering, Otto-von-Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kockentiedt
authors.affiliation: Institute of Process Engineering, Otto-von-Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hintz
authors.affiliation: Institute of Process Engineering, Otto-von-Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Tomas
authors.affiliation: Institute of Medical Psychology, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Bernhard A
authors.initials: BA
authors.lastname: Sabel
keywords: Analgesia; Blood–brain barrier; Environmental and health effects; In vivo imaging; Nanoparticles; Nanotoxicology; Polybutylcyanoacrylate; Retina