Investigation Into The Use Of Molecularly Imprinted Polymer Nanoparticles For The Delivery Of Therapeutic Compounds

Due to the increasing popularity of the use of molecularly imprinted polymer (MIP) nanoparticles as diagnostic tools, recently, interest has been directed to the use of MIP nanoparticles for use as a drug delivery system. MIPs are ideal as they are cheap to manufacture, highly stable and robust. Nanoparticles used for drug delivery work either by a triggered release of a payload under certain conditions or by controlled release out of the nanoparticles. The use of controlled release reduces the dosage of drug required to be effective on an illness or disease; it also reduces unwanted side effects caused by medication as a smaller dosage is needed compared to drugs administered by a conventional route. Initially, methods of nanoparticle sterilisation were investigated, due to the development of contamination in liquid solutions. This can cause complications when injected into live tissues. Testing found that the use of trehalose at 10mg/mL demonstrated the smallest change in nanoparticle properties, while sterilisation was found to have minimal effect on the nanoparticle properties (Chapter 2). To determine the ability of polymer nanoparticles to enter into cells, siRNA transfection studies utilising caspase-3 siRNA were carried out with the siRNA loaded onto the nanoparticles employing a charge-based interaction. The results showed that the optimal nanoparticle species was as efficient as the control transfection agent (Chapter 3). Subsequently, molecularly imprinted nanoparticles were tested for the controlled release of doxorubicin over time from different types of nanoparticles. Initially, doxorubicin imprinted magnetic core nanoparticles were tested and compared to non-imprinted nanoparticles. The results showed that the use of 2-hydroxymethyl acrylate as the functional monomer demonstrated the lowest rate of release of doxorubicin over time (Chapter 4). Solid phase synthesised were then tested with both vancomycin and EGFR binding peptide as the primary templates, the nanoparticles produced with 1mg of doxorubicin in the polymerisation mixture of the vancomycin templated nanoparticles demonstrated the lowest rate of release. With the EGFR binding peptide nanoparticles, the nanoparticles produced in aqueous solvent demonstrated the lowest rate of doxorubicin release in comparison to the organic solvent synthesised nanoparticles (Chapter 5). The effect of the primary template presence on the nanoparticles was tested and demonstrated that the presence increases the rate and amount of doxorubicin release compared to no template being present (Chapter 6). The final stage was to test the effect of different levels of cross-linking by increasing the amount of cross-linking monomer in the polymerisation mixture and found that increasing the amount of cross-linking monomer by 25 x decreased the rate and amount of doxorubicin released over time. When the effect of template presence was tested against the amount of cross-linking monomer, it was found that the presence of vancomycin caused a small increase in the rate and amount of doxorubicin released (Chapter 7). Overall the nanoparticles demonstrated significant potential for use as a delivery vessel for doxorubicin for a controlled release into the cells

Mbechsteinii_Epigenetics

R script used for the data analysis (linear regression, multiple linear regression, LOOCV)

An example of the wind cost function used for the cost simulations.

<p>Costs are shown for a range of wind speeds and angles. This example is for a sooty shearwater carrying no food payload. Angles are relative to the bird flight direction: an angle of 0° corresponds to a tailwind, 90° and 270° to cross-winds, and 180° a headwind.</p

Observed at-sea densities of sooty and short-tailed shearwaters in the Southern Ocean.

<p>A. Individual survey records (number of birds per 10-minute survey). B. Smoothed density surface fit with local scatterplot smoothing (see text). Locations of Southern Ocean fronts from north to south are shown in black: SAF-M, middle branch of the Subantarctic Front; PF-N, northern branch of the Polar Front; PF-S, southern branch of the Polar Front; SB-ACC, southern boundary of the Antarctic Circumpolar Current.</p

Sooty and short-tailed shearwater foraging in the Southern Ocean.

<p>A. Sooty shearwater tracks (grey lines) and dive locations (black dots), with the short-tailed shearwater habitat utilisation from panel B included for reference. Note the overlapping use of the Polar Front zone around 140°E. The northern and southern branches of the Polar Front (black) and the trawl transect (dotted orange) are shown. B. Short-tailed shearwater tracks from two South Australian islands (red lines) and from Wedge Island, Tasmania (green lines), and their corresponding combined habitat utilisation (background colours).</p

Simulated wind costs of long foraging trips by sooty and short-tailed shearwaters.

<p>A. Simulated wind costs (background colours) for sooty shearwaters. B. For South Australian short-tailed shearwaters. C. For Tasmanian short-tailed shearwaters. Costs are shown as percentage residuals from smooth regression of cost against distance. For example, a value of 25% indicates that the cost to visit the area in question is 25% higher than the average cost for potential foraging locations at the same geographical distance from the colony. Insets show regressions of cost against distance. The thin green lines show outward flights from the colony; the thick green lines show the simulated minimum-cost paths from the colony to representative points on the birds' foraging grounds. The orange lines show the same information for the return trips. Grey lines show the foraging components of flights (not shown in panel A for clarity). The purple lines show the direct (geodesic) routes. The northern and southern branches of the Polar Front are also shown (black).</p

Vertical water velocity at 1095m in the Southern Ocean.

<p>Twenty-year mean vertical velocity from the CSIRO Mk3.5 climate system model. The northern and southern branches of the Polar Front are shown.</p

Diel distributions of sooty shearwater diving activity.

<p>A. Distributions of sooty shearwater dives with respect to time of day. B. Dive depths with respect to time of day. The median (cross) and interquartile range (bars) are shown. Grey bars indicate dives made from 30°S–50°S, and white bars indicate dives made south of 50°S.</p

The core of the RRAP Program is founded on seven intervention research and development subprograms, including: (1) cooling and shading, (2) rubble stabilisation, (3) moving corals (larval-based restoration), (4) enhanced corals and treatments, (5) early phase intervention assessments, (6) cryopreservation, and (7) coral aquaculture and deployment.

These are supported by crosscutting R&D subprograms, engagement and regulatory frameworks, decision support, modelling, and ecological intelligence and integrated logistics and automation.</p

The coral gardening process involves the collection of coral fragments, fragmentation, a nursery phase on land or in water, and an (out)planting phase.

The coral gardening process involves the collection of coral fragments, fragmentation, a nursery phase on land or in water, and an (out)planting phase.</p