Functionalized hydrogel microparticles prepared by microfluidics and their interaction with tumour marker carbonic anhydrase IX.

Microfluidics allows precise control of the synthesis of microparticles for specific applications, where size and morphology play an important role. In this work, we have introduced microfluidic chip design with dedicated extraction and gelation sections allowing to prepare hydrogel particles in the size range of a red blood cell. The influence of the extractive channel size, alginate concentration and type of storage media on the final size of the prepared alginate microparticles has been discussed. The second part of the work is dedicated to the surface modification of prepared particles using chitosan, pHPMA and the monoclonal antibody molecule, IgG M75. The specific interaction of the antibody molecule with an antigen domain of carbonic anhydrase IX, the transmembrane tumour protein associated with several types of cancer, is demonstrated by fluorescence imaging and compared to an isotypic antibody molecule.

Molecular-level insight into hot-melt loading and drug release from mesoporous silica carriers.

Drug amorphisation by loading to inorganic mesoporous carriers represents an emerging area of improving the dissolution rate and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). In this work, for the first time, a molecular-level insight into the process of API loading to mesoporous SiO2 (silica) carriers by the hot-melt impregnation method and its subsequent release during dissolution was obtained using ATR-FTIR spectroscopic imaging. A physical mixture of ibuprofen crystals and mesoporous silica particles was heated and the dynamics of melt loading into the silica pore structure was directly observed in situ by ATR-FTIR spectroscopic imaging. The loss of crystallinity, the redistribution of the API in the silica pore network and the subsequent stabilisation of the amorphous form upon cooling were proven. The API was involved in two different kinds of molecular-level interactions: API dimers in the amorphous bulk, and individual API molecules adsorbed on the silica surface. The melt-loaded silica carriers were comprehensively characterised by DSC, SEM and dissolution tests, which proved dissolution rate enhancement due to amorphisation of the API. Drug release form the hot-melt loaded mesoporous silica carriers was observed in real time and the conditions leading to local re-crystallisation of super-saturated solution of the API were identified.

Gadolinium alginate nanogels for theranostic applications.

Synthesis of theranostic nanoparticles, which combine both therapeutic and diagnostic capabilities in one platform can be considered as a step forward personalized medicine, since it allows tracing the delivery of the drug to targeted organ. Thus, the aim of this work was to prepare gadolinium alginate gel nanoparticles (gadolinum nanogels - GdNG) by the reverse microemulsions and physical crosslinking method as the vehicles able to carry hydrophilic drugs and to be traced by the Magnetic Resonance Imaging (MRI). The average size of synthesized nanoparticles was about 110nm and the batch concentration was 1010 particles/ml. The morphology of nanogeles was visualized by Cryo-Scanning Electron Microscopy. Surface of nanogels particles was modified by the Layer-by-Layer (LbL) technique using natural polyelectrolytes. The cytotoxicity of non-modified and LbL modified nanogels was evaluated by the cellular viability quantification and cell death assessments using MTT and LDH biochemical tests, respectively. We encapsulated the model compound - fluorescent dye (Rhodamine b) in nanogels networks and proved the possibility of GdNG visualization by MRI.

Experimental study of wet granulation in fluidized bed: impact of the binder properties on the granule morphology.

In this work, the effect of the physicochemical properties of aqueous hydroxypropyl-cellulose (HPC) binder solutions and different pharmaceutical excipients (mannitol and anhydrous CaHPO(4)) on the agglomeration kinetics and granule properties were investigated. First, a particle size distribution (PSD) analysis together with a detailed analysis of morphological properties of the excipient particles were performed. Second, the viscosity, density, surface tension and size of the spray droplets of binder solutions with different HPC concentrations were determined and wetting characteristics of the binders on the excipients were measured. Third, several fluid bed wet granulation experiments were conducted for pure excipients and their blends with binder solution of different HPC concentrations in a pilot plant Wurster granulator. The observed granule growth for different binder concentrations was a strong function of the binder concentration and the excipient solubility. For mannitol, a significant "coating" period followed by a slow granule growth was observed for the case with the diluted 5% binder. The "coating" period was significantly shorter for the 10% HPC binder and did not exist for the 15% HPC for which immediate and fast granule growth was observed. For anhydrous CaHPO(4) (trademark A-TAB), no growth was observed for the 10% HPC binder and a long coating period followed by fast granule growth was observed for the 15% HPC. Simple physically based criteria were also evaluated, which employ the morphological properties of excipients (size and surface roughness) together with physical properties of the used binder for prediction of the coating versus agglomeration regime at given flow conditions (collision velocity). As expected, a preferential coalescence and growth of the mannitol granules from the blend of mannitol+A-TAB was observed. Finally, the mechanical and morphological properties of the produced granules were measured and correlated to the HPC concentration of the binder used in the experiments. A clear correlation between the granule porosity (evaluated by X-ray tomography) and the binder concentration was found for the mannitol granules.

Collisions of liquid coated solid spherical particles in a viscous fluid.

An analytical description is presented for the head-on collision of two spherical rigid particles that are coated with a thin layer of one liquid and immersed in another. Lubrication theory is used to resolve the spatio-temporal evolution of the coating surfaces, in conjunction with the fluid flow in the gap region between the particles. The analysis is carried out up to the point where the gap region has almost completely been drained; intermolecular forces are neglected. The effects of particle inertia, the ratio of particle radii, surface tension, and the viscosity ratio of the coating and carrier fluids are studied; these are parameterised by St, beta, Ca and m, respectively. The results of the present work elucidate the effect of the above-mentioned factors on the conditions under which particles rebound (assumed to occur if the distance between the particles becomes very short while the relative velocity does not vanish) or stick. In particular, summarizing flowmaps show that the likelihood of particles rebounding increases with increasing St and decreasing beta, Ca and m. On the other hand, it is shown that the force on approaching particles depends on all of these parameters in a non-monotonic manner.