In this study, a novel method was developed for tracing down reactive drug metabolites, the formation of which in the human body constitutes an important health risk as a result of their capability to bind to body proteins and DNA. Clozapine was used as a model because this drug forms both reactive and stable metabolites. Glutathione, which forms complexes with reactive metabolites, was added in order to trap reactive species of clozapine, formed by degradation in an electrochemical cell, thereby mimicking the real drug metabolism process. The method developed is based on the use of reversed-phase HPLC as a chromatographic separation technique and inductively coupled plasma-mass spectrometry (ICP-MS) for monitoring of Cl and S. Via Cl-monitoring, all metabolites of the Cl-containing clozapine can be detected, whereas S-monitoring allows for the detection of the S-containing molecule glutathione and its conjugates with reactive metabolites. The spectral overlap of the signals of S-32(+) and S-34(+) with those of (OO+)-O-16-O-16 and (OO+)-O-16-O-18, respectively, was tackled in 2 ways. On one hand, a quadrupole-based ICP-MS instrument, equipped with a dynamic reaction cell, was used. O-2 was used as a reaction gas to convert the S+ ions to a sufficient extent into the corresponding SO+ species. This did not yield optimal results, due to pronounced ArC+ signals at mass 48 and 50 upon introduction of methanol into the ICP. On the other hand, a sector-field ICP-MS instrument operated at medium mass resolution permitted interference-free monitoring of the S+-signals. A new type of skimmer cone - termed X-skimmer - was evaluated and its use resulted in a 4-fold increase in the sensitivity in a methanolic environment, providing a limit of detection of 1 mu g L-1 for S. The chromatograms obtained via HPLC-SF-ICP-MS permitted differentiation between reactive and stable metabolites. As a result, the method developed looks very promising for the detection of glutathione conjugates and shows potential for their quantification in early stages of drug development when a radiolabeled compound is not yet available

Despite its widespread application in the fields of ophthalmology, orthopedics, and dentistry and the stringent need for polymer packagings that induce in vivo tissue integration, the full potential of poly(methyl methacrylate) (PMMA) and its derivatives as medical device packaging material has not been explored yet. We therefore elaborated on the development of a universal coating for methacrylate-based materials that ideally should reveal cell-interactivity irrespective of the polymer substrate bulk properties. Within this perspective, the present work reports on the UV-induced synthesis of PMMA and its more flexible poly(ethylene glycol) (PEG)-based derivative (PMMAPEG) and its subsequent surface decoration using polydopamine (PDA) as well as PDA combined with gelatin B (Gel B). Successful application of both layers was confirmed by multiple surface characterization techniques. The cell interactivity of the materials was studied by performing live-dead assays and immunostainings of the cytoskeletal components of fibroblasts. It can be concluded that only the combination of PDA and Gel B yields materials possessing similar cell interactivities, irrespective of the physicochemical properties of the underlying substrate. The proposed coating outperforms both the PDA functionalized and the pristine polymer surfaces. A universal cell-interactive coating for methacrylate-based medical device packaging materials has thus been realized.

Here, we introduce a novel concept for the fabrication of colored materials with significantly reduced dye leaching through covalent immobilization of the desired dye using plasma-generated surface radicals. This plasma dye coating (PDC) procedure immobilizes a pre-adsorbed layer of a dye functionalized with a radical sensitive group on the surface through radical addition caused by a short plasma treatment. The non-specific nature of the plasma-generated surface radicals allows for a wide variety of dyes including azobenzenes and sulfonphthaleins, functionalized with radical sensitive groups to avoid significant dye degradation, to be combined with various materials including PP, PE, PA6, cellulose, and PTFE. The wide applicability, low consumption of dye, relatively short procedure time, and the possibility of continuous PDC using an atmospheric plasma reactor make this procedure economically interesting for various applications ranging from simple coloring of a material to the fabrication of chromic sensor fabrics as demonstrated by preparing a range of halochromic materials.

Continuous glucose monitoring (CGM) is crucial in diabetic care. Long-term CGM systems however require an accurate sensor as well as a suitable measuring environment. Since large intravenous sensors are not feasible, measuring inside the interstitial fluid is considered the best alternative. This option, unfortunately, has the drawback of a lag time with blood glucose values. A good strategy to circumvent this is to enhance tissue integration and enrich the peri-implant vasculature. Implants of different optically transparent biomaterials (poly(methyl-methacrylate) [PMMA] and poly(dimethylsiloxane) [PDMS]) -enabling glucose monitoring in the near-infrared (NIR) spectrum -were surface-treated and subsequently implanted in goats at various implantation sites for up to 3 months. The overall in vivo biocompatibility, tissue integration, and vascularization at close proximity of the surfaces of these materials were assessed. Histological screening showed similar tissue reactions independent of the implantation site. No significant inflammation reaction was observed. Tissue integration and vascularization correlated, to some extent, with the biomaterial composition. A modification strategy, in which a vascular endothelial-cadherin antibody was coupled to the biomaterials surface through a dopamine layer, showed significantly enhanced vascularization 3 months after subcutaneous implantation. Our results suggest that the developed strategy enables the creation of tissue interactive NIR transparent packaging materials, opening the possibility of continuous glucose monitoring.

The unique versatility of polymers allows them to be manufactured into both commonly used house-hold items and specialised medical devices. ‘Plastic’ windows and contact lenses form one such example, as both are manufactured from the same material, called poly(methyl methacrylate), or PMMA.