Idebenone (IDE) is an antioxidant drug active at the level of the central nervous system (CNS), whose poor water solubility limits its clinical application. An IDE/2-hydroxypropyl-β-cyclodextrin (IDE/HP-β-CD) inclusion complex was investigated by combining experimental methods and theoretical approaches. Furthermore, biological in vitro/ex vivo assays were performed. Phase solubility studies showed an AL type diagram, suggesting the presence of a 1:1 complex with high solubility. Scanning electron microscopy (SEM) allowed us to detect the morphological changes upon complexation. The intermolecular interactions stabilizing the inclusion complex were experimentally characterized by exploring the complementarity of Fourier-transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) with mid-infrared light, Fourier-transform near-infrared (FT-NIR) spectroscopy, and Raman spectroscopy. From the temperature evolution of the O–H stretching band of the complex, the average enthalpy ΔHHB of the hydrogen bond scheme upon inclusion was obtained. Two-dimensional (2D) rotating frame Overhauser effect spectroscopy (ROESY) analysis and computational studies involving molecular modeling and molecular dynamics (MD) simulation demonstrated the inclusion of the quinone ring of IDE inside the CD ring. In vitro/ex vivo studies evidenced that complexation produces a protective effect of IDE against the H2O2-induced damage on human glioblastoma astrocytoma (U373) cells and increases IDE permeation through the excised bovine nasal mucosa.
This study was aimed at preparing and characterizing solid lipid nanoparticles loading rutin (RT-SLNs) for the treatment of oxidative stress-induced diseases. Phospholipon 80H® as a solid lipid and Polysorbate 80 as surfactant were used for the SLNs preparation, using the solvent emulsification/diffusion method. We obtained spherical RT-SLNs with low sizes, ranging from 40 to 60 nm (hydrodynamic radius) for the SLNs prepared starting from 2% and 5% (w/w) theoretical amount. All prepared formulations showed negative zeta-potential values. RT was efficiently encapsulated within SLNs, obtaining high encapsulation efficiency and drug content percentages, particularly for SLNs prepared with a 5% theoretical amount of RT. In vitro release profiles and analysis of the obtained data applying different kinetic models revealed Fickian diffusion as the main mechanism of RT release from the SLNs. The morphology of RT-SLNs was characterized by scanning electron microscopy (SEM), whereas the interactions between RT and the lipid matrix were investigated by Raman spectroscopy, evidencing spectral modifications of characteristic bands of RT due to the establishment of new interactions. Finally, antioxidant activity assay on human glioblastoma astrocytoma (U373) culture cells showed a dose-dependent activity for RT-SLNs, particularly at the highest assayed dose (50 μM), whereas the free drug showed the lesser activity.
1 December 2017 in Environmental Toxicology and Pharmacology
The Directive 2013/35/EU establishes standards for workers exposed to static and time varying magnetic fields. These limits are based on ICNIRP guidelines expressed in terms of the electric field induced in the body. The complexity of this measurement led to theoretical models being developed. In this study, the experimental evaluation included varying magnetic field exposures for two classes of MRI workers. The measurements are conducted on four different MRI Systems including one 0.35 T, two 1.5 T, and one 3.0 T. Pocket magnetic dosimeters were used and it was carried out during routine conditions, emergency conditions, and cold-head maintenance/substitution. The acquired data has been processed and the corresponding dB/dt curves have been computed as the first time derivative of the dataset. The weighted peak approach was also implemented for the compliance assessment with regulatory limits. The dB/dt peak values have been compared with the reference level (RL) proposed by ICNIRP. The results show that the RL always exceeds during measurements on the 3.0 T scanner and sometimes on 1.5 T. In light of the foregoing, the diffusion of ultra-high field MRI scanners involves the introduction of behavioral rules that could be more useful than a numerical action level.
We propose here a spectroscopic method to diagnose and differentiate inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD) with pediatric onset, in a complete noninvasive way without performing any duodenal biopsy. In particular, the Raman technique was applied to proteic extract from fecal samples in order to achieve information about molecular vibrations that can potentially furnish spectral signatures of cellular modifications occurring as a consequence of specific pathologic conditions. The attention was focused on the investigation of the amide I region, quantitatively accounting the spectral changes in the secondary structures by applying deconvolution and curve-fitting. Inflammation is found to give rise to a significant increasing of the nonreducible (trivalent)/reducible (divalent) cross-linking ratio of the protein network. This parameter revealed an excellent marker in order to distinguish IBD subjects from non-IBD ones, and, among IBD patients, to differentiate between UC and CD. The proposed methodology was validated by statistical analysis using the receiver operating characteristic (ROC) curve.