PROTEIN-TRIGGERED SUSTAINED DRUG RELEASE CONTROLLED BY APTAMERS BOUND TO OLIGOMER-CROSSLINKED ALGINATE

Sustained drug release systems provide many advantages over traditional delivery methods such as extending the time in which the drug is found to be within an effective concentration within the therapeutic window, which decreases the frequency of administration of the drug, and increases patient compliance. Research using polyacrylamide crosslinked by oligomers containing an aptamer sequence, has demonstrated a pulsatile release over 50 minutes triggered by a 2 mM target adenosine concentration. This thesis aims to build off this concept by designing a system that delivers in a sustained manner when triggered by micromolar target concentrations reflective of disease in vivo, using macromolecular targets. For example, the disease wet age related macular degeneration (wet AMD) is associated with increased concentrations of the protein vascular endothelial growth factor (VEGF-A) – a macromolecule. Patients with wet AMD would benefit from the implantation of devices or microspheres that release drugs in a sustained manner in response to local VEGF concentrations. In this thesis, we hypothesize that the protein lysozyme, used to demonstrate proof-of-concept, could trigger the increased release of drugs from oligomer-crosslinked alginate. The objectives are to (i) demonstrate sustained release from alginate, (ii) design oligomer crosslinked alginate that degrades in response to lysozyme, and then (iii) use these systems to control the release of FITC-dextran with and without lysozyme. A series of control experiments and analyses were used to optimize the crosslinking of alginate by annealed oligomers. The cumulative release of FITC-dextran (MW 20,000) from oligomer crosslinked alginate increased by 3.4 μg when lysozyme (3 μM) was introduced at 48 hours, as opposed to controls which released only 0.2 μg. FITC-loaded alginate microspheres coated by oligomer-crosslinked alginate released 15% more FITC-dextran over 120 hours when placed into 3 μM of lysozyme than without lysozyme. Controls of alginate crosslinked with PEG or control oligomers (without a lysozyme aptamer sequence) had no changes in release with lysozyme. The incorporation of a lysozyme aptamer onto oligomers used to crosslink alginate disks or alginate coatings on microspheres resulted in different diffusion and release of FITC-dextran into PBS with or without lysozyme. This approach could be adapted for the delivery of drugs to diseases with specific protein profiles such as wet AMD.

ESTUDIO ESTRUCTURAL DE SEMICONDUCTORES USADOS EN APLICACIONES FOTOVOLTAICAS

Se presenta un estudio de las propiedades estructurales de los semiconductores Bi2S3, SnS, SnS2, SnS:Bi, Cu3BiS3 y Cu(In,Ga)Se2 (CIGS) usados como capa absorbente en dispositivos optoelectrónicos. Todas las muestras fueron crecidas por procesos de co-evaporación de sus especies metálicas sobre sustratos de vidrio. El efecto de las condiciones de preparación sobre las propiedades estructurales y composición química han sido analizados y obtenidos a partir de difracción de rayos-X (XRD) y espectroscopia de electrones Auger (AES). Los resultados revelan que todos los compuestos crecen con estructura ortorrómbica, a diferencia del SnS2 y el CIGS, que crecen con estructura hexagonal y tetragonal, respectivamente. Los resultados composicionales revelaron que a partir de la deconvolución de sus picos se encontraron fases asociadas a Cu2Se y In2Se3

Valorization of bio-alcohols into added value chemicals

The present research work focused on the valorisation and upgrading of bio-ethanol over heterogeneous catalysts in a lab-scale continuous gas-flow system. In the Unibo laboratories, catalytic tests have been carried out in the temperature range 300-600°C by feeding an ethanol/He mixture in the reactor. After choosing the reaction conditions, ion-exchanged hydroxyapatite with transition metals (i.e., Fe, Cu) and alkaline earth metal (i.e., Sr) have been synthesized and tested. The Sr-HAP catalyst led to the formation of a complex reaction mixture the composition of which need further optimization in order to fill the requisite to be used as fuel-blend. Then, some zirconium-oxide based catalysts have been prepared through two different methods, precipitation and hydrothermal, by varying some synthetic parameters (i.e., pH, the nature of the base) and by adding a transition metal as dopant agent (i.e., Ti and Y). The presence of a dopant into the zirconia structure favoured the stabilization of the tetragonal or cubic phase against the monoclinic one. Interestingly, 5%mol Ti-doped zirconia exhibited a different catalytic behaviour yielding diethyl ether as major product at 300°C, while all the others samples produced mainly ethylene. Then, the effect of acid-base properties of sepiolite, using alkali metals (i.e., Na, K, Cs) with different metal loading (i.e., 2, 4, 5, 7, 14 wt%) as promoters, and of the redox properties of sepiolite-supported CuO or NiO, on the catalytic conversion of ethanol into n-butanol has been investigated. Thermal treated sepiolite samples mainly acted as acid catalyst, yielding preferentially the dehydration products of ethanol (ethylene and diethyl ether). Best results in terms of activity (ethanol conversion, 59%) and n-butanol selectivity (30%) where obtained at 400ºC and a contact time, W/F, of 2 g/mL·s over the catalyst consisting of sepiolite calcined at 500ºC modified with 7 wt% of cesium.