Werner Hintz

Toxicity of polymeric nanoparticles in vivo and in vitro

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.

Glass Spheres: Functionalization, Surface Modification and Mechanical Properties

Hydrophobic micro-glass particles were obtained by chemical modification with organosilanes. Particles were treated by peroxymonosulfuric acid to obtain a hydrophilic surface, which was the first step of the modification process. Different silanes were used, each of them with a different functional group, effecting variable degrees of hydrophobicity. The successful chemical modification process was established using Fourier transform infrared spectroscopy (FTIR) and water drop interaction with the modified particles surfaces. The morphology of the modified particles was studied using scanning electron microscope (SEM). The degree of the hydrophobicity was established with static contact angle measurements. The microscopic adhesion and particle contact properties of the comparatively stiff (amorphous) micro-glass beads and the macroscopic powder flow behavior were investigated with ring shear tests and evaluated by constitutive models on physical basis.

The synthesis and use of steric-stabilised titania nanoparticles in Pickering-emulsion preparation

We employed the well-accepted sol-gel process to synthesise spherical titania nanoparticles of narrow size range 290 nm to 1,600 nm by mixing reactants such as titanium tetra isopropoxide (precursor), organic solvents (ethanol and isopropanol) and for the steric stabilisation, commercial surfactants (Brij 30, Brij 72, Brij 76 and Marlinat 242/28). Experimentally, the size distribution of synthesised titania nanoparticles vary with type and concentration of reactants, process sequence and duration at rest after synthesis. Also, Pickering-emulsion samples were prepared by stabilising oil-in-water emulsions with the synthesised titania nanoparticles. The study is meant to contribute to the research on preparation of Pickering-emulsion, further processed as sunscreen lotions in the cosmetic industry.

Evaluation of Toxicity and Neural Uptake In Vitro and In Vivo of Superparamagnetic Iron Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIO-NPs) have great potential to be used in different pharmaceutical applications, due to their unique and versatile physical and chemical properties. The aim of this study was to quantify in vitro cytotoxicity of dextran 70,000-coated SPIO-NPs labelled/unlabelled with rhodamine 123, in C6 glioma cells and primary hippocampal neural cells. In addition, we analyzed the in vitro and in vivo cellular uptake of labelled SPIO-NPs. The nanoparticles, with average size of 10–50 nm and polydispersity index of 0.37, were synthesized using Massart’s co-precipitation method. The concentration-dependent cytotoxicity was quantified by using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Intracellular localization of SPIO-NPs was detected by confocal laser microscopy. In vivo confocal neuroimaging (ICON) was performed on male Wistar rats after intravitreal injection followed by ex vivo retina whole mount analysis. When used for in vitro testing concentrations in the range of diagnostic and therapeutic dosages, SPIO-NPs proved to be non-cytotoxic on C6 glioma cells for up to 24 h incubation time. The hippocampal cell culture also did not show impaired viability at low doses after 24 h incubation. Our results indicate that our dextran-coated SPIO-NPs have the potential for in vivo drug delivery applications.