Inhaled drug delivery is ideal for treatment of asthma and chronic obstructive pulmonary disease (COPD) as it allows a local action of the medication at the disease site. Biodegradable polymeric nanoparticles which might allow extended/sustained release of inhaled drugs are synthesized using various methods however; these do not permit high encapsulation efficiency for hydrophilic drugs. The aim of the project was to test the hypothesis that it was possible to develop an efficient method for the co-encapsulation of a hydrophilic and lipophilic drug (theophylline and budesonide respectively) into nanoparticles. In order to improve the loading efficiency of both hydrophilic and hydrophobic drugs, a modified double emulsification solvent diffusion (DESD) method was developed and both co-encapsulated and mono-encapsulated nanoparticles (containing either drug) were synthesized. Improved loading efficiency, studied using high performance liquid chromatography (HPLC), for both drugs was obtained. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) showed that particles were in the sub-micron range (150-400 nm). Measurement of zeta potential showed that the particles had a negative surface charge and additionally Fourier-transform infra-red (FT-IR) spectroscopy confirmed that this was due to the polymer and no drug was adsorbed on the external surface of the nanoparticles. Resemblance of nanoparticles thermograms, obtained using differential scanning calorimetry (DSC), to those of the polymer alone suggested successful encapsulation of the drugs. Stability studies of the drug encapsulated nanoparticles conducted at different temperatures indicated that storage conditions of 2-8°C over a period of 6 months showed minimal changes in the particle size, zeta potential and morphological characteristics of the nanoparticles. Storage (of the nanoparticles) at 40°C over the course of 6 months resulted in larger variations on the particle size and zeta potential but also loss of morphological features of the nanoparticles, suggestive of changes in the polymer state at this temperature. Franz diffusion cells were used to study the release of drugs from the nanoparticles over 24 hours at room temperature and at 37oC. The results showed that release of theophylline and budesonide from nanoparticles was biphasic and sustained compared to release of drug from solutions containing an equivalent concentration of drug. The effect of the nanoparticles on the viability of airway epithelial cells was studied using a human bronchial epithelial cell line (16HBE14o-) using a 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The nanoparticles had no significant effect ii on cell viability except at the highest concentration of the suspension studied (5 mg/mL) (P < 0.05). The permeability of 16HBE14o- cells, cultured at an air-liquid interface, to theophylline and budesonide applied in solution and as mono-encapsulated and co-encapsulated nanoparticles was studied. The nanoparticles and drug solutions did not affect the tight junctions of the cells and similar to the results obtained in the Franz diffusion cells, both drugs crossed the cells more slowly when applied as nanoparticles in comparison to the solutions. To study deposition of the nanoparticles; nebulized suspensions of the nanoparticles in de-ionized water and dry powder formulations using different grades of lactose were compared. The prepared formulations were studied using a multi-stage liquid impinger (MSLI). The results indicated that drug deposition was greatest in stages 1 and 2 of the MSLI where particle size was greater than 6.8μm from the dry powder formulations in contrast to deposition throughout the five stages of the MSLI from the nebulized suspension. Morphological assessment of the dry powder formulations using SEM showed nanoparticles adhered to the lactose but also included nanoparticles in the absence of lactose and vice versa. In conclusion, theophylline and budesonide nanoparticles were successfully formulated using PLA by application of the DESD method. Nanoparticles possessed desired physicochemical properties including submicron size range and negatively charged surface; however a higher loading efficiency of the hydrophobic drug was obtained despite modifications to the DESD method. Low toxicity of the nanoparticles to human bronchial epithelial cells and sustained release over a period of 24 hours was achieved. Nanoparticles were delivered successfully in the target site at a desired particle size range when formulated as nebulized suspensions.

The aim of the study was to describe how patient understanding and attitude to the effects of rheumatoid arthritis on the foot, and the services available to help limit this, influences self reporting of foot problems. Referral to podiatry was occurring at a stage in the disease process too late to instigate certain preventative interventions. Preliminary fieldwork highlighted that the responsibility for the instigation of this locally lay with the patient. Literature supports the inclusion of podiatry within the multidisciplinary rheumatology team and early foot assessment with regular monitoring. There was a gap in the literature relating to the effectiveness of patient self-reporting in terms of foot health and the implications of relying on this approach.

In the UK, there are now more people over state pensionable age than there are children. With the UK Government‟s plans to raise state pension age in line with increasing longevity, many older people may need further paid employment into what would formerly be termed their retirement years. The concept of retirement is becoming an unknown entity that brings challenges and uncertainty. It is a UK Government priority to address the need for cost-effective, innovative initiatives to promote health and well-being of older people, preparing them effectively for their retirement years. Occupational therapists are ideally placed to collaborate with such individuals to attain optimal levels of health, functioning and life satisfaction through meaningful occupation.

The expanding field of stroke medicine lacks foundation if it fails to embrace the infrastructure of experiential evidence, instrumental in shaping future services by identification of need. Potential seriousness of fleeting illness, like transient ischaemic attack (TIA) a precursor for stroke with devastating health and social consequences may be underestimated. Lack of awareness leads to under-reporting and not accessing timely medical attention and the latter could obviate serious consequences of long-term disability. Informed choice and opportunity to avert these circumstances by lifestyle changes needs to be available to all to take responsibility for health. The literature gap of lived experience of illness needs narrowing, particularly transient illnesses like TIA that comes under the umbrella of stroke yet is a discrete illness of very short duration and nonetheless alarming. Health and social care lifetime costs of stroke are immense. Implications for evidence-based clinical practice concern influencing lifestyle changes, a role that physiotherapists could take to help avert disastrous costly outcomes consequent upon modifiable risks. This lead to a research question of: What is the lived experience of a TIA? The intention of this study was to position the research within current UK National Health Service (NHS) policy considering the historical and philosophical background and psychosocial theories of health and illness. A tension exists between increasing public awareness of health matters and improved health against unhealthy behaviours of sedentary lifestyles and poor diets leading to lifestyle diseases with budgetary implications. Multiple behaviour theories affect lifestyle change. One trigger is evidence-based information with sufficient impact to awaken a response to take responsibility for health. Influences are education, knowledge, patient-centred care, partnership, choice, empowerment, consumerism and professional roles and identity. Studies of other transient illnesses were considered.

Back pain is a common and costly disorder affecting 80% of the population, with 80-90% of the symptoms reported to have no pathological cause and it is suggested that this non-specific low back pain can be improved by the adoption of proper posture and body mechanics during normal daily life.

This thesis explores perceptions of nursing held by a range of stakeholders at the beginning of the 21st century. Using a constructivist methodology, this study locates nursing within the current context of healthcare, acknowledging the historical and socio-political influences which have contributed to shaping nursing’s identity and nursing work. The use of a case study approach as the mode for constructivist inquiry draws on an understanding of this approach as a ‘depth examination of an instance’ (Lincoln and Guba, 1985 p.360). This recognises the contemporary and time bound nature of the study, located in a time of modernisation and change within both nursing and the wider National Health Service.

Mechanisms of cochlea excitation and amplification were investigated experimentally across a range of mammalian species. Distortion product otoacoustic emissions (DPOAEs) are used to clinically assess hearing. DPOAEs recorded from the ears of human subjects in the presence of a low frequency, high level tone were compared with similar recordings made from guinea pigs. Both guinea pig and human data were found to originate from a common cochlear nonlinearity; the Boltzmann model of DPOAE generation at the output of a spatially localised single-saturating non-linearity. Accordingly, the guinea pig cochlea can be used as a human model system for the study of DPOAE generation.

Novel steroidal oestrogens, that incorporate some of the structural motifs of non-steroidal antioestrogens, were synthesised and tested for their actions on the BK channel. These novel compounds were first checked for purity and structure using, where appropriate, 1H NMR, 13C NMR, IR spectroscopy, mass spectroscopy, thin layer chromatography, melting point analysis, elemental analysis and X-ray crystallography. Using Oestrone as the starting compound, the following five novel compounds were synthesised; DME-Oestrone, Quat-DME-Oestrone, DME-Oestradiol, Quat-DME-Oestradiol and Oestrone-Oxime. Two of the derivatives, Quat-DME-Oestrone and Quat-DME-Oestradiol, incorporated a quaternary ammonium side-chain making them membrane impermeable.

Cancer is one of the leading causes of death in the world (only second to heart disease in developed countries). It is a multifactorial disease that is characterised by the unregulated growth of the atypical forms of the body’s own cells and intrusion and spread of these cells from the primary site to other areas in the body. It is rare for cancer to cause death by the functional failure of the primary organ affected and the clinical consequences of cancer are indirect relating to the bulk of the tumour or the invasion of tissues both local and distant.

The repair of peripheral nerve lesions presents a common clinical challenge, with those injured suffering from an array of debilitating symptoms and sensory or motor handicaps. The current method of repairing peripheral nerve lesions involves the use of nerve autografts or artificial nerve repair conduits to bridge the gap between the two ends of the damaged nerve. However, results from the use of these techniques rarely produce full functional recovery. Several studies have shown that carbon nanotubes (CNTs) can be used as a successful substrate for the growth and guidance of neurons. These data suggest CNTs could be used as a neural tissue scaffold that may be incorporated into the lumen of existing nerve repair conduits to enhance axonal guidance at the nanoscale. Despite the substantial interest in the use of CNTs as a biomaterial in neurobiology, very little is understood about the interactions of CNT’s with neurons. The aim of this research project is to 1) provide an assessment of CNT biocompatibility with cells of the peripheral nervous system and 2) assess the ability of a CNT substrate to support neurite outgrowth.