Project 1. Markers of gastric emptying in intensive care patients
Generally, drugs are better absorbed in the small intestine, because of the larger surface area, than in the stomach. Therefore, faster gastric emptying would be expected to increase drug absorption. A good correlation has been found between gastric emptying time and the peak plasma concentration for paracetamol. Therefore, in the literature, gastric emptying is usually measured by the paracetamol absorption test. Caffeine has also been suggested as a suitable marker for gastric emptying. We will compare the suitability of these two drugs as markers for gastric emptying and use these findings in a study of atorvastatin absorption in intensive care patients.
In previous work, we collected blood samples from intensive care patients who received oral paracetamol and caffeine and the caffeine levels have already been measured. In this project we will use an established high performance liquid chromatography (HPLC) assay to measure the plasma paracetamol levels. These data will be subjected to mathematical modelling and the pharmacokinetics of caffeine and paracetamol will be compared to assess their relative rates of gastric emptying.
This project entails a combination of bench work and mathematical analysis.
Project 2. Novel drug delivery formulations
There is tremendous research and commercial interest in topical drug delivery because it is non-invasive and largely avoids first-pass metabolism often seen in oral administration. However, the number of molecules suitable for this route is small. Various strategies are used to increase skin penetration rates and to expand the range of suitable drugs. In this project, we will use some advanced formulations (e.g. hydrogels, nanoemulsions) to improve topical delivery of selected drugs.
Experiments will be carried out by applying drug formulations to excised human skin in Franz diffusion cells. High performance liquid chromatography assays will be developed and used to analyse drug concentrations. This will allow us to calculate the rate of diffusion of drug molecules though the skin.
This project involves mainly bench work and some straightforward analysis.
Project 3. Multiphoton microscopic imaging and analysis
Humans can be exposed to nanoparticles in the environment, in cosmetic products, or in the future, in therapeutic substances. There is concern that these particles may penetrate the skin and have damaging effects. We can image the penetration of fluorescent substances, including nanoparticles, with our multiphoton microscope. It also allows us to measure any metabolic changes to the skin itself in response to penetrating substances.
In this project, we will apply substances (e.g. sunscreens containing zinc oxide nanoparticles) to the skin of human volunteers and collect images with the microscope. The digital images will then be analysed by advanced software.
This project involves a high degree of data analysis.
Project 4. Iontophoretic delivery of gold nanoparticles
A recent article (Dohnert et al, Int J Nanomed 2012;7:1651-7) reports the use of a combination of gold nanoparticles and diclofenac to treat inflammation in a rat model. These substances were delivered through the skin by the use of direct current (iontophoresis). Such combined treatment may be applicable to humans, but it is not known whether iontophoresis is able
to push the gold nanoparticles through human skin. We have already shown that gold nanoparticles do not penetrate human skin under normal conditions (i.e., without any external force such as direct current).
In this project, we will use iontophoresis to measure the rate of penetration of gold nanoparticles through excised human skin and synthetic membrane. The gold concentration will be measured by spectrophotometry.
This project requires mainly bench work, with some technical skill. Data analysis should be straightforward.
Project 5. Water desorption from human skin.
The skin, in particular the thin layer of dead cells on its surface known as the stratum corneum, forms a very effective barrier to the penetration of substances from the outside. It also regulates the loss of water from the inside in order to maintain homeostasis. The rate of water evaporation from the surface of the skin is called 'transepidermal water loss', or TEWL and we have an instrument to measure this. The TEWL value reflects the condition of the skin and indicates whether it is dry, damaged, diseased, aged, etc. The aim of this project is to establish a mathematical model to describe the mechanism of water loss from the skin. This will provide information about exactly how this layer of skin cells functions as a barrier.
In this project, we will measure the TEWL in the skin of human volunteers. With the help of our research associate, Associate Professor Yuri Anissimov, we will use these data to develop a mathematical model of 'water desorption' from the skin surface.
This project requires some technical skill to obtain TEWL measurements and an interest in mathematics and model development.