Characterization of Ion-Exchange Fibers for Controlled Drug Delivery

Increasing attention has been focused on methods that deliver pharmacologically active compounds (e.g. drugs, peptides and proteins) in a controlled fashion, so that constant, sustained, site-specific or pulsatile action can be attained. Ion-exchange resins have been widely studied in medical and pharmaceutical applications, including controlled drug delivery, leading to commercialisation of some resin based formulations. Ion-exchangers provide an efficient means to adjust and control drug delivery, as the electrostatic interactions enable precise control of the ion-exchange process and, thus, a more uniform and accurate control of drug release compared to systems that are based only on physical interactions. Unlike the resins, only few studies have been reported on ion-exchange fibers in drug delivery. However, the ion-exchange fibers have many advantageous properties compared to the conventional ion-exchange resins, such as more efficient compound loading into and release from the ion-exchanger, easier incorporation of drug-sized compounds, enhanced control of the ion-exchange process, better mechanical, chemical and thermal stability, and good formulation properties, which make the fibers attractive materials for controlled drug delivery systems. In this study, the factors affecting the nature and strength of the binding/loading of drug-sized model compounds into the ion-exchange fibers was evaluated comprehensively and, moreover, the controllability of subsequent drug release/delivery from the fibers was assessed by modifying the conditions of external solutions. Also the feasibility of ion-exchange fibers for simultaneous delivery of two drugs in combination was studied by dual loading. Donnan theory and theoretical modelling were applied to gain mechanistic understanding on these factors. The experimental results imply that incorporation of model compounds into the ion-exchange fibers was attained mainly as a result of ionic bonding, with additional contribution of non-specific interactions. Increasing the ion-exchange capacity of the fiber or decreasing the valence of loaded compounds increased the molar loading, while more efficient release of the compounds was observed consistently at conditions where the valence or concentration of the extracting counter-ion was increased. Donnan theory was capable of fully interpreting the ion-exchange equilibria and the theoretical modelling supported precisely the experimental observations. The physico-chemical characteristics (lipophilicity, hydrogen bonding ability) of the model compounds and the framework of the fibrous ion-exchanger influenced the affinity of the drugs towards the fibers and may, thus, affect both drug loading and release. It was concluded that precisely controlled drug delivery may be tailored for each compound, in particularly, by choosing a suitable ion-exchange fiber and optimizing the delivery system to take into account the external conditions, also when delivering two drugs simultaneously.

Properties of intramuscular connective tissue in pork and poultry with reference to weakening of structure

The most common connective tissue research in meat science has been conducted on the properties of intramuscular connective tissue (IMCT) in connection with eating quality of meat. From the chemical and physical properties of meat, researchers have concluded that meat from animals younger than physiological maturity is the most tender. In pork and poultry, different challenges have been raised: the structure of cooked meat has weakened. In extreme cases raw porcine M. semimembranosus (SM) and in most turkey M. pectoralis superficialis (PS) can be peeled off in strips along the perimysium which surrounds the muscle fibre bundles (destructured meat), and when cooked, the slices disintegrate. Raw chicken meat is generally very soft and when cooked, it can even be mushy. The overall aim of this thesis was to study the thermal properties of IMCT in porcine SM in order to see if these properties were in association with destructured meat in pork and to characterise IMCT in poultry PS. First a 'baseline' study to characterise the thermal stability of IMCT in light coloured (SM and M. longissimus dorsi in pigs and PS in poultry) and dark coloured (M. infraspinatus in pigs and a combination of M. quadriceps femoris and M. iliotibialis lateralis in poultry) muscles was necessary. Thereafter, it was investigated whether the properties of muscle fibres differed in destructured and normal porcine muscles. Collagen content and also solubility of dark coloured muscles were higher than in light coloured muscles in pork and poultry. Collagen solubility was especially high in chicken muscles, approx. 30 %, in comparison to porcine and turkey muscles. However, collagen content and solubility were similar in destructured and normal porcine SM muscles. Thermal shrinkage of IMCT occurred at approximately 65 °C in pork and poultry. It occurred at lower temperature in light coloured muscles than in dark coloured muscles, although the difference was not always significant. The onset and peak temperatures of thermal shrinkage of IMCT were lower in destructured than in normal SM muscles, when the IMCT from SM muscles exhibiting ten lowest and ten highest ultimate pH values were investigated (onset: 59.4 °C vs. 60.7 °C, peak: 64.9 °C vs. 65.7 °C). As the destructured meat was paler than normal meat, the PSE (pale, soft, exudative) phenomenon could not be ruled out. The muscle fibre cross sectional area (CSA), the number of capillaries per muscle fibre CSA and per fibre and sarcomere length were similar in destructured and normal SM muscles. Drip loss was clearly higher in destructured than in normal SM muscles. In conclusion, collagen content and solubility and thermal shrinkage temperature vary between porcine and poultry muscles. One feature in the IMCT could not be directly associated with weakening of the meat structure. Poultry breast meat is very homogenous within the species.

Atomic Layer Deposition of Electroluminescent ZnS, SrS, and BaS Thin Films

The light emitted by flat panel displays (FPD) can be generated in many different ways, such as for example alternating current thin film electroluminescence (ACTFEL), liquid crystal display (LCD), light emitting diode (LED), or plasma display panel (PDP) technologies. In this work, the focus was on ACTFEL devices and the goal was to develop new thin film processes for light emitting materials in ACTFEL devices. The films were deposited with the atomic layer deposition (ALD) method, which has been utilized in the manufacturing of ACTFEL displays since the mid-1980s. The ALD method is based on surface-controlled self-terminated reactions and a maximum of one layer of the desired material can be prepared during one deposition cycle. Therefore, the film thickness can be controlled simply by adjusting the number of deposition cycles. In addition, both large areas and deep trench structures can be covered uniformly. During this work, new ALD processes were developed for the following thin film materials: BaS, CuxS, MnS, PbS, SrS, SrSe, SrTe, SrS1-xSex, ZnS, and ZnS1-xSex. In addition, several ACTFEL devices were prepared where the light emitting material was BaS, SrS, SrS1-xSex, ZnS, or ZnS1-xSex thin film that was doped with Ce, Cu, Eu, Mn, or Pb. The sulfoselenide films were made by substituting the elemental selenium for sulfur on the substrate surface during film deposition. In this way, it was possible to replace a maximum of 90% of the sulfur with selenium, and the XRD analyses indicated that the films were solid solutions. The polycrystalline BaS, SrS, and ZnS thin films were deposited at 180-400, 120-460, and 280-500 °C, respectively, and the processes had a wide temperature range where the growth rate of the films was independent of the deposition temperature. The electroluminescence studies showed that the doped sulfoselenide films resulted in low emission intensity. However, the emission intensities and emission colors of the doped SrS, BaS, and ZnS films were comparable with those found in earlier studies. It was also shown that the electro-optical properties of the different ZnS:Mn devices were different as a consequence of different ZnS:Mn processes. Finally, it was concluded that because the higher deposition temperature seemed to result in a higher emission intensity, the thermal stability of the reactants has a significant role when the light emitting materials of ACTFEL devices are deposited with the ALD method.

A New Rare-Gas Compound: HXeOXeH

Rare-gas chemistry is of growing interest, and the recent advances include the "insertion" of a Xe atom into OH and water in the rare-gas hydrides HXeO and HXeOH. The insertion of Xe atoms into the H-C bonds of hydrocarbons was also demonstrated for HXeCC, HXeCCH and HXeCCXeH, the last of which was the first rare-gas hydride containing two rare-gas atoms. We describe the preparation and characterization of a new rare-gas compound, HXeOXeH. HXeOXeH was prepared in solid xenon by photolysis of a suitable precursor, for example water, and subsequent mobilization of the photoproducts. The experimental identification was carried out by FTIR spectroscopy, isotopic substitution and by use of various precursors. The photolytical and thermal stability of the new rare-gas hydride was also studied. The experimental work was supported by extensive quantum chemical calculations provided by our co-workers. HXeOXeH forms in a cryogenic xenon matrix from neutral O and H atoms in a two-step diffusion-controlled process involving HXeO as an intermediate [reactions (1) and (2)]. This formation mechanism is unique in that a rare-gas hydride is formed from another rare-gas hydride. H + Xe + O → HXeO (1) HXeO + Xe + H → HXeOXeH (2) Similarly to other rare-gas hydrides, HXeOXeH has a strongly IR-active H-Xe stretching vibration, allowing its spectral detection at 1379.3 cm-1. HXeOXeH is a very high-energy metastable species, yet thermally more stable than many other rare-gas hydrides. The calculated bending barrier of 0.57 eV, is not enough to explain the observed stability, and HXeOXeH might be affected by additional stabilization from the solid xenon environment. Chemical bonding between xenon and environmentally abundant species like water is of particular importance due to the “missing-xenon” problem. The relatively high thermal stability of HXeOXeH compared to other oxygen containing rare-gas compounds is relevant in this respect. Our work also raises the possibility of polymeric (–Xe–O)n networks, similarly to the computationally studied (XeCC)n polymers.

Phytoplankton ecology of subarctic lakes in Finnish Lapland

Climate is warming and it is especially seen in arctic areas, where the warming trend is expected to be greatest. Arctic freshwater ecosystems, which are a very characteristic feature of the arctic landscape, are especially sensitive to climate change. They could be used as early warning systems, but more information about the ecosystem functioning and responses are needed for proper interpretation of the observations. Phytoplankton species and assemblages could be especially suitable for climate-related studies, since they have short generation times and react rapidly to changes in the environment. In addition, phytoplankton provides a good tool for lake classifications, since different species have different requirements and tolerance ranges for various environmental factors. The use of biological indicators is especially useful in arctic areas, were many of the chemical factors commonly fall under the detection limit and therefore do not provide much information about the environment. This work brings new information about species distribution and dynamics of arctic freshwater phytoplankton in relation to environmental factors. The phytoplankton of lakes in Finnish Lapland and other European high-altitude or high-latitude areas were compared. Most lakes were oligotrophic and dominated by flagellated species belonging to chrysophytes, cryptophytes and dinoflagellates. In Finnish Lapland cryptophytes were of less importance, whereas desmids had high species richness in many of the lakes. In Pan-European scale, geographical and catchment-related factors were explaining most of the differences in species distributions between different districts, whereas lake water chemistry (especially conductivity, SiO2 and pH) was most important regionally. Seasonal and interannual variation of phytoplankton was studied in subarctic Lake Saanajärvi. Characteristic phytoplankton species in this oligotrophic, dimictic lake belonged mainly to chrysophytes and diatoms. The maximum phytoplankton biomass in Lake Saanajärvi occurs during autumn, while spring biomass is very low. During years with heavy snow cover the lake suffers from pH drop caused by melt waters, but the effects of this acid pulse are restricted to surface layers and last for a relatively short period. In addition to some chemical parameters (mainly Ca and nutrients), length of the mixing cycle and physical factors such as lake water temperature and thermal stability of water column had major impact on phytoplankton dynamics. During a year with long and strong thermal stability, the phytoplankton community developed towards an equilibrium state, with heavy dominance of only a few taxa for a longer period of time. During a year with higher windiness and less thermal stability, the species composition was more diverse and species with different functional strategies were able to occur simultaneously. The results of this work indicate that although arctic lakes in general share many common features concerning their catchment and water chemistry, large differences in biological features can be found even in a relatively small area. Most likely the lakes with very different algal flora do not respond in a similar way to differences in the environmental factors, and more information about specific arctic lake types is needed. The results also show considerable year to year differences in phytoplankton species distribution and dynamics, and these changes are most likely linked to climatic factors.

Atomic scale engineering of carbon nanotubes

Carbon nanotubes, seamless cylinders made from carbon atoms, have outstanding characteristics: inherent nano-size, record-high Young’s modulus, high thermal stability and chemical inertness. They also have extraordinary electronic properties: in addition to extremely high conductance, they can be both metals and semiconductors without any external doping, just due to minute changes in the arrangements of atoms. As traditional silicon-based devices are reaching the level of miniaturisation where leakage currents become a problem, these properties make nanotubes a promising material for applications in nanoelectronics. However, several obstacles must be overcome for the development of nanotube-based nanoelectronics. One of them is the ability to modify locally the electronic structure of carbon nanotubes and create reliable interconnects between nanotubes and metal contacts which likely can be used for integration of the nanotubes in macroscopic electronic devices. In this thesis, the possibility of using ion and electron irradiation as a tool to introduce defects in nanotubes in a controllable manner and to achieve these goals is explored. Defects are known to modify the electronic properties of carbon nanotubes. Some defects are always present in pristine nanotubes, and naturally are introduced during irradiation. Obviously, their density can be controlled by irradiation dose. Since different types of defects have very different effects on the conductivity, knowledge of their abundance as induced by ion irradiation is central for controlling the conductivity. In this thesis, the response of single walled carbon nanotubes to ion irradiation is studied. It is shown that, indeed, by energy selective irradiation the conductance can be controlled. Not only the conductivity, but the local electronic structure of single walled carbon nanotubes can be changed by the defects. The presented studies show a variety of changes in the electronic structures of semiconducting single walled nanotubes, varying from individual new states in the band gap to changes in the band gap width. The extensive simulation results for various types of defect make it possible to unequivocally identify defects in single walled carbon nanotubes by combining electronic structure calculations and scanning tunneling spectroscopy, offering a reference data for a wide scientific community of researchers studying nanotubes with surface probe microscopy methods. In electronics applications, carbon nanotubes have to be interconnected to the macroscopic world via metal contacts. Interactions between the nanotubes and metal particles are also essential for nanotube synthesis, as single walled nanotubes are always grown from metal catalyst particles. In this thesis, both growth and creation of nanotube-metal nanoparticle interconnects driven by electron irradiation is studied. Surface curvature and the size of metal nanoparticles is demonstrated to determine the local carbon solubility in these particles. As for nanotube-metal contacts, previous experiments have proved the possibility to create junctions between carbon nanotubes and metal nanoparticles under irradiation in a transmission electron microscope. In this thesis, the microscopic mechanism of junction formation is studied by atomistic simulations carried out at various levels of sophistication. It is shown that structural defects created by the electron beam and efficient reconstruction of the nanotube atomic network, inherently related to the nanometer size and quasi-one dimensional structure of nanotubes, are the driving force for junction formation. Thus, the results of this thesis not only address practical aspects of irradiation-mediated engineering of nanosystems, but also contribute to our understanding of the behaviour of point defects in low-dimensional nanoscale materials.