Peter Adriaensens

POLYMERS FOR COLON SPECIFIC DRUG DELIVERY

Azo-linked polymeric prodrugs of 5-aminosalicylic acid (5-ASA) were prepared and evaluated in simulated human intestinal microbial ecosystem. Release of 5-ASA was demonstrated. Polyamides containing azo groups in the backbone were prepared and tested in vitro in a reductive buffer or in the bioreactor medium. It was demonstrated that for the hydrophobic polymer reduction stops at the hydrazine stage whereas for a hydrophilic analogue reduction with formation of amines occurred.

Efficient formation, isolation and characterization of poly(3-alkylthiophene) nanofibres: probing order as a function of side-chain length

Efficient fibre formation for all regioregular poly(3-alkylthiophene)s (P3ATs) with alkyl chain lengths (A) between 3 and 9 carbon atoms has been accomplished in several solvents. It was observed that for the aliphatic and (chlorinated) aromatic hydrocarbon solvents used, the solvent refractive index offers some rationale to predict the feasibility of a solvent for fibre formation. The fibres were separated from remaining non-organised polymer by centrifugation. This enabled the characterisation of the isolated fibres in function of alkyl chain length (A) with TEM, AFM, XRD and UV-Vis spectroscopy. The fibres are 20 ± 5 nm wide and 0.5 to >4 µm long and mainly crystallize in the common type I crystal phase. The order within the fibres was probed with XRD, SAED, and UV-Vis and was found to strongly improve with increasing alkyl chain length in going from P33T to P35T, resulting in a longer conjugation length. For P35T to P39T the improvement in order is only marginal. Fibres from P37T were found to mainly crystallize in a crystal phase slightly different from type I that we refer to as type I′. This new crystal structure has a lattice constant a that is marginally shorter than that of phase I and a slightly longer lattice constant b of 4.0 A and thus in XRD can hardly be distinguished from phase I. It is furthermore characterized by a blue-shifted absorption band in UV-Vis spectroscopy. The type I′ fibres were converted into normal type I fibres in the solid state at 70 °C and in solution around 50 °C.

Protein Engineering For Directed Immobilization

Much effort has been put into the optimization of the functional activity of proteins. For biosensors this protein functional optimization will increase the biosensors sensitivity and/or selectivity. However, the strategy chosen for the immobilization of the proteins to the sensor surface might be equally important for the development of sensor surfaces that are optimally biologically active. Several studies published in recent years show that the oriented immobilization of the bioactive molecules improves the sensors properties. In this review, we discuss the state of the art of the different protein immobilization strategies that are commonly used today with a special focus on biosensor applications. These strategies include nonspecific immobilization techniques either by physical adsorption, by covalent coupling, or by specific immobilization via site-specifically introduced tags or bio-orthogonal chemistry. The different tags and bio-orthogonal chemistry available and the techniques to site-specifically introduce these groups in proteins are also discussed.

In-line NIR spectroscopy for the understanding of polymer-drug interaction during pharmaceutical hot-melt extrusion

The aim was to evaluate near-infrared spectroscopy for the in-line determination of the drug concentration, the polymer-drug solid-state behaviour and molecular interactions during hot-melt extrusion. Kollidon® SR was extruded with varying metoprolol tartrate (MPT) concentrations (20%, 30% and 40%) and monitored using NIR spectroscopy. A PLS model allowed drug concentration determination. The correlation between predicted and real MPT concentrations was good (R(2)=0.97). The predictive performance of the model was evaluated by the root mean square error of prediction, which was 1.54%. Kollidon® SR with 40% MPT was extruded at 105°C and 135°C to evaluate NIR spectroscopy for in-line polymer-drug solid-state characterisation. NIR spectra indicated the presence of amorphous MPT and hydrogen bonds between drug and polymer in the extrudates. More amorphous MPT and interactions could be found in the extrudates produced at 135°C than at 105°C. Raman spectroscopy, DSC and ATR FT-IR were used to confirm the NIR observations. Due to the instability of the formulation, only in-line Raman spectroscopy was an adequate confirmation tool. NIR spectroscopy is a potential PAT-tool for the in-line determination of API concentration and for the polymer-drug solid-state behaviour monitoring during pharmaceutical hot-melt extrusion.

Synthesis of poly(p-phenylene vinylene) materials via the precursor routes

Poly(p-phenylene vinylene)s (PPVs) are an important class of conjugated polymer materials that have in the last few years gained significant interest in the polymer community. (Precursor) Synthesis routes to obtain high-molecular weight PPVs are reviewed with respect to the applicability of the reactions towards specific synthesis goals and materials as well as structural integrity of the obtained polymers, which affect the applicability of these compounds in electronic devices.

Macro‐ and micro‐anatomical, histological and computed tomography scan characterization of the nasopalatine canal

AIM To determine the human anatomic variability of the nasopalatine canal and determine its characteristics using an anatomical, histological and computed tomography (CT) scan evaluation. MATERIALS AND METHODS Measurements for the canal characteristics were carried out on 163 dry human skulls and 120 upper jaw spiral CT scans, taken from patients for pre-operative planning purposes of implant placement in the incisor region. Furthermore, four human cadaver specimens were imaged using a high-resolution magnetic resonance imaging (HR-MRI) unit. Afterwards, these specimens were serially sectioned for histological examination to evaluate the nasopalatine canal region and its content. RESULTS The nasopalatine canal anatomy showed a large variability in morphology and dimensions, with the canal branching in up to four canals at the level of the nose. The canal diameter was on average 3.3 mm (+/-0.9 mm SD), and typically enlarged by age and male gender (p<0.05). HR-MRI and histological sections enabled to identify the neurovascular structures within the canals. CONCLUSIONS The large anatomic variations, the increased canal dimensions with age and the neurovascular canal content are all factors favouring a thorough three-dimensional planning before surgery, such as implant placement, of the anterior maxillary region.

Femoral neck trabecular microstructure in ovariectomized ewes treated with calcitonin: MRI microscopic evaluation.

Ovariectomy induces deterioration of the trabecular structure in the femoral neck of ewes, as depicted by MR microscopic imaging. This structural deterioration is prevented by salmon calcitonin treatment.

Visualisation of the kinetics of macrophage infiltration during experimental autoimmune encephalomyelitis by magnetic resonance imaging

Macrophages are considered to be the predominant effector cells in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Ultra small particles of iron oxide (USPIO) can be used to detect macrophage infiltrates in the CNS with magnetic resonance imaging (MRI). Here, we investigated whether the kinetics of lesion formation in EAE can be visualised by altering the time point of USPIO injection and the time interval between particle injection and MRI. When USPIO are systemically injected 24 h before MRI, hypo intense regions are detected in different brain regions depending on the disease stage. These regions correspond to sites of macrophage infiltration. A more complete visualisation of sites of inflammation is accomplished by USPIO injection at disease onset and postponing MRI to top of disease. This study demonstrates that the distribution pattern and amount of inflammatory lesions detected with USPIO, depends on timing of USPIO administration and subsequent MRI. These findings are important for a correct application and interpretation of USPIO dependent contrast imaging of CNS inflammation.

Development and characterization of mucoadhesive chitosan films for ophthalmic delivery of cyclosporine A

Ocular chitosan films were prepared in order to prolong ocular delivery of cyclosporine A. The mucoadhesive films were prepared using the solvent casting evaporation method. A 2(4) full factorial design was used to evaluate the effect of 4 preparation parameters on the film thickness, swelling index and mechanical properties. Moreover, uniformity of content and in vitro drug release were investigated. Possible interactions between the film excipients were studied by FTIR analysis. In vitro experiments were performed in order to evaluate the cytotoxicity and anti-inflammatory activity of the chitosan films. Film thickness, water uptake, mechanical properties and in vitro release of cyclosporine A were dependent on film composition, especially on the amount of plasticizer. Lower drug release was measured from chitosan films containing a higher amount of plasticizer as glycerol decreased the swelling of chitosan films. FTIR spectra suggest a reorganization of hydrogen bonds between chitosan chains in the presence of glycerol and cyclodextrins. None of the film formulations showed significant cytotoxicity as compared to the negative control using human epithelial cells (HaCaT). Cyclosporine A dispersed in the various film formulations remained anti-inflammatorily active as significant suppression of interleukin-2 secretion in concanavalin A stimulated Jurkat T cells was measured.

Quantitative magnetic resonance imaging study of water uptake by polyamide 4,6

Abstract Magnetic resonance imaging (MRI) and NMR relaxation experiments are used to study the water absorption by polyamide 4,6 (PA46) plates. Despite the higher crystallinity, PA46 absorbs more water as compared to the polyamides 6 and 6,6 (PA6 and PA66). Relaxation measurements demonstrate that the volume averaged molecular mobility ( T 2 H ) of the absorbed water molecules in PA46 is higher than in PA6 and PA66. Quantitative relaxation results of water saturated PA46 further suggest fast exchange between free water and water molecules bound via hydrogen bonds to amide groups. MRI reveals a gradual decrease in the amount and the T 2 H relaxation behaviour of water from the surface towards the core part of PA46 plates. This can be explained by the very high crystallisation rate of PA46, which prevents the close coupling of amide groups in the amorphous phase and results in a larger mean distance between the amide groups, especially in the outer part of the PA46 plates. Density measurements (WAXS and gradient column) show an increase of the density of the amorphous phase during annealing, resulting in a lower water uptake and a lower mobility of the absorbed water molecules.