The present thesis is focused on the study of Organic Semiconducting Single Crystals (OSSCs) and crystalline thin films. In particular solution-grown OSSC, e.g. 4-hdroxycyanobenzene (4HCB) have been characterized in view of their applications as novel sensors of X-rays, gamma-rays, alpha particles radiations and chemical sensors. In the field of ionizing radiation detection, organic semiconductors have been proposed so far mainly as indirect detectors, i.e. as scintillators or as photodiodes. I first study the performance of 4HCB single crystals as direct X-ray detector i.e. the direct photon conversion into an electrical signal, assessing that they can operate at room temperature and in atmosphere, showing a stable and linear response with increasing dose rate. A dedicated study of the collecting electrodes geometry, crystal thickness and interaction volume allowed us to maximize the charge collection efficiency and sensitivity, thus assessing how OSSCs perform at low operating voltages and offer a great potential in the development of novel ionizing radiation sensors. To better understand the processes generating the observed X-ray signal, a comparative study is presented on OSSCs based on several small-molecules: 1,5-dinitronaphthalene (DNN), 1,8-naphthaleneimide (NTI), Rubrene and TIPS-pentacene. In addition, the proof of principle of gamma-rays and alpha particles has been assessed for 4HCB single crystals. I have also carried out an investigation of the electrical response of OSSCs exposed to vapour of volatile molecules, polar and non-polar. The last chapter deals with rubrene, the highest performing molecular crystals for electronic applications. We present an investigation on high quality, millimeter-sized, crystalline thin films (10 – 100 nm thick) realized by exploiting organic molecular beam epitaxy on water-soluble substrates. Space-Charge-Limited Current (SCLC) and photocurrent spectroscopy measurements have been carried out. A thin film transistor was fabricated onto a Cytop® dielectric layer. The FET mobility exceeding 2 cm2/Vs, definitely assess the quality of RUB films.

This thesis work is focused on the use of selected core-level x-ray spectroscopies to study semiconductor materials of great technological interest and on the development of a new implementation of appearance potential spectroscopy. Core-level spectroscopies can be exploited to study these materials with a local approach since they are sensitive to the electronic structure localized on a chemical species present in the sample examined. This approach, in fact, provides important micro-structural information that is difficult to obtain with techniques sensitive to the average properties of materials. In this thesis work we present a novel approach to the study of semiconductors with core-level spectroscopies based on an original analysis procedure that leads to an insightful understanding of the correlation between the local micro-structure and the spectral features observed. In particular, we studied the micro-structure of Hydrogen induced defects in nitride semiconductors, since the analysed materials show substantial variations of optical and electronic properties as a consequence of H incorporation. Finally, we present a novel implementation of soft x-ray appearance potential spectroscopy, a core-level spectroscopy that uses electrons as a source of excitation and has the great advantage of being an in-house technique. The original set-up illustrated was designed to reach a high signal-to-noise ratio for the acquisition of good quality spectra that can then be analyzed in the framework of the real space full multiple scattering theory. This technique has never been coupled with this analysis approach and therefore our work unite a novel implementation with an original data analysis method, enlarging the field of application of this technique.

III-nitride materials are very promising for high speed electronics/optical applications but still suffer in performance due to problems during high quality epitaxial growth, evolution of dislocation and defects, less understanding of fundamental physics of materials/processing of devices etc. This thesis mainly focus on GaN based heterostructures to understand the metal-semiconductor interface properties, 2DE(H)G influence on electrical and optical properties, and deep level states in GaN and InAlN, InGaN materials. The detailed electrical characterizations have been employed on Schottky diodes at GaN and InAl(Ga)N/GaN heterostructures in order to understand the metal-semiconductor interface related properties in these materials. I have observed the occurrence of Schottky barrier inhomogenity, role of dislocations in terms of leakage and creating electrically active defect states within energy gap of materials. Deep level transient spectroscopy method is employed on GaN, InAlN and InGaN materials and several defect levels have been observed related to majority and minority carriers. In fact, some defects have been found common in characteristics in ternary layers and GaN layer which indicates that those defect levels are from similar origin, most probably due to Ga/N vacancy in GaN/heterostructures. The role of structural defects, roughness has been extensively understood in terms of enhancing the reverse leakage current, suppressing the mobility in InAlN/AlN/GaN based high electron mobility transistor (HEMT) structures which are identified as key issues for GaN technology. Optical spectroscopy methods have been employed to understand materials quality, sub band and defect related transitions and compared with electrical characterizations. The observation of 2DEG sub band related absorption/emission in optical spectra have been identified and proposed for first time in nitride based polar heterostructures, which is well supported with simulation results. In addition, metal-semiconductor-metal (MSM)-InAl(Ga)N/GaN based photodetector structures have been fabricated and proposed for achieving high efficient optoelectronics devices in future.

III-nitrides are wide-band gap materials that have applications in both electronics and optoelectronic devices. Because to their inherent strong polarization properties, thermal stability and higher breakdown voltage in Al(Ga,In)N/GaN heterostructures, they have emerged as strong candidates for high power high frequency transistors. Nonetheless, the use of (Al,In)GaN/GaN in solid state lighting has already proved its success by the commercialization of light-emitting diodes and lasers in blue to UV-range. However, devices based on these heterostructures suffer problems associated to structural defects. This thesis primarily focuses on the nanoscale electrical characterization and the identification of these defects, their physical origin and their effect on the electrical and optical properties of the material. Since, these defects are nano-sized, the thesis deals with the understanding of the results obtained by nano and micro-characterization techniques such as atomic force microscopy(AFM), current-AFM, scanning kelvin probe microscopy (SKPM), electron beam induced current (EBIC) and scanning tunneling microscopy (STM). This allowed us to probe individual defects (dislocations and cracks) and unveil their electrical properties. Taking further advantage of these techniques,conduction mechanism in two-dimensional electron gas heterostructures was well understood and modeled. Secondarily, origin of photoluminescence was deeply investigated. Radiative transition related to confined electrons and photoexcited holes in 2DEG heterostructures was identified and many body effects in nitrides under strong optical excitations were comprehended.

Organic semiconductors have great promise in the field of electronics due to their low cost in term of fabrication on large areas and their versatility to new devices, for these reasons they are becoming a great chance in the actual technologic scenery. Some of the most important open issues related to these materials are the effects of surfaces and interfaces between semiconductor and metals, the changes caused by different deposition methods and temperature, the difficulty related to the charge transport modeling and finally a fast aging with time, bias, air and light, that can change the properties very easily. In order to find out some important features of organic semiconductors I fabricated Organic Field Effect Transistors (OFETs), using them as characterization tools. The focus of my research is to investigate the effects of ion implantation on organic semiconductors and on OFETs. Ion implantation is a technique widely used on inorganic semiconductors to modify their electrical properties through the controlled introduction of foreign atomic species in the semiconductor matrix. I pointed my attention on three major novel and interesting effects, that I observed for the first time following ion implantation of OFETs: 1) modification of the electrical conductivity; 2) introduction of stable charged species, electrically active with organic thin films; 3) stabilization of transport parameters (mobility and threshold voltage). I examined 3 different semiconductors: Pentacene, a small molecule constituted by 5 aromatic rings, Pentacene-TIPS, a more complex by-product of the first one, and finally an organic material called Pedot PSS, that belongs to the branch of the conductive polymers. My research started with the analysis of ion implantation of Pentacene films and Pentacene OFETs. Then, I studied totally inkjet printed OFETs made of Pentacene-TIPS or PEDOT-PSS, and the research will continue with the ion implantation on these promising organic devices.

The nasal route is highly promising for the delivery of drugs exerting local effects in the nose or for therapeutic molecules having systemic or CNS effect. This is attributed to the fact that the nasal epithelium is highly vascularized and permeable, which ensures rapid absorption of the drug. The limitation of short residence time of the formulations in the nose and poor bioavailability of hydrophilic drugs could be overcome by the inclusion of bioadhesive agents into formulation. The main objective of this study was to develop novel bioadhesive microspheres and liposomes entrapping the anti-Parkinson drugs ropinirole hydrochloride (RH). The microspheres were prepared via spray drying in combination with chitosan or sodium alginate and the liposomes were prepared using the ethanol-based proliposome method. This study has investigated the potential of powdered mucoadhesive microparticles and liquid liposomes for nasal delivery via Miat® nasal insufflator and nasal spray devices respectively. Optimum mucoadhesive chitosan microparticles were prepared by co-spray drying of chitosan glutamate and ropinirole hydrochloride (90:10 w/w). Characterization studies have revealed that the drug following spray drying was amorphous and the microparticles were spherical and offered drug entrapment efficiency values in the range of 93 - 99%. The optimum formulation provided maximum swelling capacity and slowest drug release. Ex vivo toxicity study using isolated sheep nasal mucosa proved the safety of the optimized formulations for intranasal delivery. Investigation of powder delivery demonstrated that the Miat® nasal insufflator could deliver 90% of the dose with the first puff regardless of the loading weight used to fill the capsule fitted into the nasal device. The spray cloud had elongated shape and was homogenous; this is expected to enhance the impaction of the formulation in the nose following delivery from the nasal device. The properties of sodium alginate microparticles prepared via spray drying were highly dependent on inlet temperature of the spray drier, affecting particle morphology and product yield percent. The best performing particles were obtained when the inlet temperature was 140oC. Alginate to RH ratio had marked effect on particle size (2.60 - 4.37µm), entrapment efficiency (101 – 109%), physical state of the encapsulated RH, and morphology and surface smoothness of the particles as shown by scanning electron microscopy (SEM). In vitro drug release profile showed the amount of sodium alginate in formulations has controlled the rate of drug release. Results revealed that RH-alginate microparticles in 90:10 w/w polymer to drug ratio was the best performing spray dried formulation. Toxicity study proved safety of RH loaded sodium alginate for intranasal delivery. In contrast to RH-chitosan microparticles, particle trajectories was found from the cloud generated from emitted powder and laser diffraction demonstrated that powder was less likely to deposit in the lower respiratory tract owing to particle agglomeration. Ethanol-based proliposome technology produced oligolamellar liposomes from lipid ethanolic solutions as revealed by transmission electron microscopy (TEM). The resultant liposomes entrapped approximately 23.30% of the drug. Using five different bioadhesive agents, inclusion of any of these agents (0.2% w/v) caused a decrease in drug entrapment except for carboxymethyl chitosan which had no effect on the drug entrapment (25.97%). Investigation of aerosolized liposome dispersion using a range of nasal spray devices demonstrated integrity of liposomes were not changed (i.e particle size, Span, and drug entrapment efficiency were unaffected) and RH-loaded liposomes were efficiently delivered from the devices. In conclusion, the finding of this study explored mucoadhesive microspheres entrapped the anti-Parkinson drug, RH, and can potentially be applicable for nasal delivery to enhance nose to brain transport using nasal insufflator for improvement of the symptoms of Parkinson disease and Restless legs syndrome. Similar findings using nasal sprays were found for liposomes. In vivo studies are required in the future to determine the amount of the drug that may reach the blood circulation and brain.

Substituted indoles (2-arylindoles) and related structures are known to exhibit potent anti-cancer activity against human breast cancer cell lines, and a range of other therapeutic targets. This activity, and other factors such as their biological activity, the fact that they are privileged structures, and the presence of the indole nucleus in various commercial anti-cancer drugs led to the choosing of indoles for the current study as a starting point for the development of new treatments against glioma. Investigation began on determining the anti-cancer activity of a variety of indoles against glioma cell lines (1321N1 and U87MG) using a number of different cell-based assays and also to compare them with conventional anti-cancer drugs. The aim was to find potent anti-cancer compound(s), amongst the compounds tested, and by studying its preliminary structure-activity-relationships (SAR), try to determine how the active compound(s) may be exerting their effects. The SAR screening was divided into two main groups: indoles without a 2-aryl group and indoles with a 2-aryl group. The most potent compound identified, and its analogues, were further tested on the non-cancerous SVGp12 cell line to check for specificity of these indoles towards cancer cells, wherein it was found that these compounds were not specific to any particular cell type. Furthermore, activity was also observed for the best lead compound in the glioblastoma short-term culture, IN859, in which it gave a relatively low micromolar IC50 value (400 μM). The results indicated that the anti-cancer activity of these compounds started within 2 h and therefore it was speculated that the mechanism of action of these compounds might work through the generation of reactive oxygen species (ROS). A ROS-detection kit was used to demonstrate this hypothesis, a result which was later corroborated using flow cytometry, and also provided quantitative analysis of the amount of ROS generated. It was further hypothesised that in the cells studied, autophagy was mediated due to excessive ROS generation. This was also confirmed over a similar time course by quantifying the amount of fluorescence generated in the 1321N1 and U87MG cell lines when labelled with acridine orange (a dye used to detect the formation of autophagosomes during autophagy) using flow cytometry. Moreover, the use of an autophagy inhibitor, 3-methyladenine, was shown to inhibit autophagy in these cell lines, again validating this hypothesis. In conclusion, it has been demonstrated that the ability of certain substituted privileged indoles possessing a 2-aryl group and having an attached –OH group to it may have a rapid, deleterious effect on the viability of a primary short term culture (IN859) and glioma cell lines (1321N1 and U87MG). The mechanism of action of these indoles to cause cell death may be via the generation of ROS, leading to cell death initiated by autophagy. Another short separate study was also performed in order to investigate the anti-cancer activity of an anionic host defence peptide, Cn-AMP2, on the above mentioned cell lines. This peptide was found to exhibit a modest cytostatic effect on both the cell lines but at higher concentrations (> 1 mM) and only when the serum concentrations were weaned down from 10 % to 2.5 %.

In the past two decades only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action. Aspirin is one of the most widely used drugs, successfully taken as an analgesic, antipyretic, anti-inflammatory agent and for prevention of strokes and ischemic diseases. The effects on cell viability, proliferation, apoptosis and migration of aspirin and aspirin derivatives were tested on primary glioblastoma cell cultures, BTNW911 and BTNW 914, and the well-established cell lines, SVG-p12, 1321N1, GOS-3, U87 MG, using the PrestoBlue assay, CFDA-SE, PI/annexin V, and live imaging receptively. The effects on cell viability following 24 and 48 hour incubation of four aspirin derivatives (PN508, PN517, PN526 and PN529) were compared to cisplatin, aspirin and di-aspirin, establishing IC50 values, showing PN517 to be the most potent analogue, and in some cases greater efficacy than cisplatin. Aspirin analogues showed greatest efficacy in the first 24 hours, while cisplatin increased in efficacy with time showing a lower IC50 value in all cell lines at 48 hours. Cell proliferation was assessed over 3 to 10 days, with each treatment decreasing proliferation and the largest effect of PN517 found in BTNW914 cells. PN517 treatment decreased the population of G0/G1 phase cells in cell cycle analysis, decreased cyclin D1 and EGFR activation, and total EGFR expression. Apoptosis was induced by PN517 in a concentration and time dependent manner in both the cell lines and short term cultures, with activation of both intrinsic and extrinsic pathways. Finally, PN517 reduced migration in both the Boyden chamber and scratch assays, but did not inhibit invasion. In conclusion, these data support the further development of PN517 as a novel therapeutic drug for the treatment of glioma.

The field of Bioelectronics deals with the integration of electronics and biology, and possesses a tremendous potential regarding the improvement of the quality of life of millions of people. Thanks to their favorable properties, conjugated polymers have proven to be very suitable materials for the bridging of such diverse worlds. In particular, poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate), or PEDOT:PSS, is nowadays considered a benchmark material for bioelectronics applications. The aim of the present work is to give a detailed characterization of the physical and electrochemical properties of PEDOT:PSS thin films, and to prove the potentialities of this material both for the sensing of bioanalytes, through the development of innovative electrochemical sensors, and for tissue engineering applications, through the development of redox-active substrates that can control the replication of living cells. In this work, the development of all PEDOT:PSS-based organic electrochemical transistors (OECTs) is presented. The sensing efficiency of these devices was optimized in terms of sensitivity and limit of detection (LOD) through the investigation of the effect of device geometry, thickness, and operating voltages. An electrochemical characterization of these devices was carried out as well, in order to clarify the processes involved in the device operation. Furthermore, the operation of these devices as electrochemical sensors was tested on several analytes, obtaining in most cases a performance suitable for real applications. The development and characterization of a different kind of devices realized using the same material, redox-active substrates for applications in tissue engineering, is then presented. The effect of a change in the redox state of these PEDOT:PSS films on cell growth is assessed using two cell lines, human dermal fibroblasts (hDF) and human tumoral glioblastoma multiforme cells (T98G), finding that the cell proliferation rate has a clear dependence on the electrochemical state of its substrate.

Research into responsive polymeric insulin delivery systems for the management of diabetes mellitus is gaining increasing interest due to the rise in the incidence rate and the burden of daily multiple subcutaneous insulin injections that needs to be endured by the patient. The present study attempted to formulate a nanoparticulate glucose responsive insulin delivery system from a natural polymer chitosan, using a safe glucose sensor, phenyl boronic acid (PBA), which is known to interact with glucose. In the present project, a new method for the production of chitosan tripolyphosphate (TPP) nanoparticles via ultrasonication was developed and optimised. The electrostatic method of tagging PBA onto chitosan was unsuccessful, but the method of N-reductive alkylation of introducing the PBA was successful. Evidence of PBA bonding on to chitosan was assessed by FTIR, ToF-SIMS, DSC and glucose adsorption sensitivity measurements. Glucose adsorption sensitivity to PBA-bonded chitosan polymer was directly related to the amount of PBA functionality within the conjugates and the physical nature of the matrices (porous or crystalline) as revealed by scanning electron microscopy (SEM). The nanoparticles showed glucose concentration dependent swelling with swelling decrease at a glucose concentration above 2.5mg/ml. Encapsulation of insulin into the nanoparticulate matrix was achieved by both the ionotropic gelation and polyelectrolyte complexation methods. Smaller particles with z-average between 140 – 150nm, lower Pdi and zeta potential between 17.5-19.1mV were characteristic of particles produced by PEC, whilst slightly larger particles with z-averages between 170-200nm, higher Pdi and zeta potential between +17.6-21.6mV were noticed for the particles produced by ionotropic gelation. Higher encapsulation of insulin of about 90% was achieved using the PEC method as compared to 34% from the ionotropic gelation series. The amount of drug encapsulated in both methods was pH dependent. In vitro xxi glucose dependent insulin release studied on PEC formulations showed a glucose and fructose concentration dependent release which was affected by the buffer system used. Lower insulin release from higher concentration of the sugars was attributed to the formation of bidentate interaction between the diols in the sugar and PBA, which restricts further expansion of the nanoparticles and hence reduces insulin release. This was confirmed by the SEM images of the nanoparticles after exposure to buffer, glucose and fructose in buffers at pH 7.4. Nanoparticles exposed to fructose showed more spherical and intact matrices whilst the buffer samples showed fragmented particles. The samples exposed to glucose showed some degree of fragmentation but not high as compared to that of nanoparticles exposed to buffer. The release of insulin from this formulation was therefore dependent on a complex interplay between the components of the buffer and the amount of sugar present.