Design and evaluation of novel microencapsulation technologies to enhance delivery of Ciclosporin

Drug delivery systems influence the various processes of release, absorption, distribution and elimination of drug. Conventional delivery methods administer drug through the mouth, the skin, transmucosal areas, inhalation or injection. However, one of the current challenges is the lack of effective and targeted oral drug administration. Development of sophisticated strategies, such as micro- and nanotechnology that can integrate the design and synthesis of drug delivery systems in a one-step, scalable process is fundamental in advancing the limitations of conventional processing techniques. Thus, the objective of this thesis is to evaluate novel microencapsulation technologies in the production of size-specific and target-specific drug-loaded particles. The first part of this thesis describes the utility of PDMS and silicon microfluidic flow focusing devices (MFFDs) to produce PLGA-based microparticles. The formation of uniform droplets was dependent on the surface of PDMS remaining hydrophilic. However, the durability of PDMS was limited to no more than 1 hour before wetting of the microchannel walls with dichloromethane and subsequent swelling occurred. Critically, silicon MFFDs revealed very good solvent compatibility and was sufficiently robust to withstand elevated fluid flow rates. Silicon MFFDs facilitated experiments to run over days with continuous use and re-use of the device with a narrower microparticle size distribution, relative to conventional production techniques. The second part of this thesis demonstrates an alternative microencapsulation technology, SmPill® minispheres, to target CsA delivery to the colon. Characterisation of CsA release in vitro and in vivo was performed. By modulating the ethylcellulose:pectin coating thickness, release of CsA in-vivo was more effectively controlled compared to current commercial CsA formulations and demonstrated a linear in-vitro in-vivo relationship. Coated minispheres were shown to limit CsA release in the upper small intestine and enhance localised CsA delivery to the colon.

An exploration through interview and drawings of the experiences of patients diagnosed with oral cancer across their cancer trajectory

Background: The treatment of oral cancer is complex and lengthy. Curative treatment implies a combination of surgery, radiotherapy and chemotherapy. The main goal of treatment is to guarantee long-term tumour free survival with as little functional and cosmetic damage. Despite progress in developing these strategies, cancers of the oral cavity continue to have high mortality rates that have not improved dramatically over the past ten years. Aim: The aim of this study was to uniquely explore the dynamic changes in the physical, psychological, social and existential experiences of newly diagnosed patients with oral cancer at two points across their cancer illness trajectory i.e. at the time of diagnosis and at the end of treatment. Methodology: A qualitative prospective longitudinal design was employed. Non-probability purposive sampling allowed the recruitment of 10 participants. The principal data collection method used was a digital audio taped semi-structured interview along with drawings produced by the participants. Analysis: Data was analysed using latent content analyses. Summary: Three ‘dynamic’ themes, physical, psychosocial and existential experiences were revealed that interact and influence each other in a complex and compound whole. These experiences are present at different degrees and throughout the entire trajectory of care. Patients have a number of specific concerns and challenges that cannot be compartmentalised into unitary or discrete aspects of their daily lives. Conclusion & Implications: An understanding of the patient’s experience of their illness at all stages of the disease trajectory, is essential to inform service providers’ decision making if the delivery of care is to be client centred. Dynamic and fluctuating changes in the patient’s personal experience of the cancer journey require dynamic, energetic and timely input from health care professionals.

Electromagnetic tracking and steering for catheter navigation

This thesis explores the use of electromagnetics for both steering and tracking of medical instruments in minimally invasive surgeries. The end application is virtual navigation of the lung for biopsy of early stage cancer nodules. Navigation to the peripheral regions of the lung is difficult due to physical dimensions of the bronchi and current methods have low successes rates for accurate diagnosis. Firstly, the potential use of DC magnetic fields for the actuation of catheter devices with permanently magnetised distal attachments is investigated. Catheter models formed from various materials and magnetic tip formations are used to examine the usefulness of relatively low power and compact electromagnets. The force and torque that can be exerted on a small permanent magnet is shown to be extremely limited. Hence, after this initial investigation we turn our attention to electromagnetic tracking, in the development of a novel, low-cost implementation of a GPS-like system for navigating within a patient. A planar magnetic transmitter, formed on a printed circuit board for a low-profile and low cost manufacture, is used to generate a low frequency magnetic field distribution which is detected by a small induction coil sensor. The field transmitter is controlled by a novel closed-loop system that ensures a highly stable magnetic field with reduced interference from one transmitter coil to another. Efficient demodulation schemes are presented which utilise synchronous detection of each magnetic field component experienced by the sensor. The overall tracking accuracy of the system is shown to be less than 2 mm with an orientation error less than 1°. A novel demodulation implementation using a unique undersampling approach allows the use of reduced sample rates to sample the signals of interest without loss of tracking accuracy. This is advantageous for embedded microcontroller implementations of EM tracking systems. The EM tracking system is demonstrated in the pre-clinical environment of a breathing lung phantom. The airways of the phantom are successfully navigated using the system in combination with a 3D computer model rendered from CT data. Registration is achieved using both a landmark rigid registration method and a hybrid fiducial-free approach. The design of a planar magnetic shield structure for blocking the effects of metallic distortion from below the transmitter is presented which successfully blocks the impact of large ferromagnetic objects such as operating tables. A variety of shielding material are analysed with MuMetal and ferrite both providing excellent shieling performance and an increased signal to noise ratio. Finally, the effect of conductive materials and human tissue on magnetic field measurements is presented. Error due to induced eddy currents and capacitive coupling is shown to severely affect EM tracking accuracy at higher frequencies.