Therapeutics Research Centre

Professor Mike Roberts

Professor Roberts is an NHMRC Senior Principal Research Fellow, Professor of Clinical Pharmacology & Therapeutics at The University of Queensland and Professor of Therapeutics & Pharmaceutical Science at the University of South Australia with 40 years research experience. He established and is Director of the Therapeutics Research Centre (TRC), based in the Translational Research Institute (Brisbane) and the Basil Hetzel Institute at The Queen Elizabeth Hospital (Adelaide). His research interests include: drug delivery (skin, eye, oral, mucosa), non-invasive imaging and modelling, drug ADMET, pharmacokinetics, liver and pancreas, respiratory, cancer, natural therapeutics, burns and health services delivery. TRC work has been continuously supported by competitively funded grants, government partnerships and industry partnerships.

He actively works with industry, government, academia and clinicians, locally and internationally. His research outputs include: 6 research books, 428 peer reviewed research publications and 49 book chapters; 180 invited international talks and >$31m in grant funding, including current NHMRC Program and Project grants and an ARC Discovery Project Grant.

He has been awarded both ASCEPT’s RAND and APSA’s medals, is a former APSA President, a Fellow of the Australian College of Pharmacy, an APVMA Fellow in Nanoscience and a co-recipient of the 2011 ARC Eureka Prize for Excellence in Research by an Interdisciplinary Team.

Dr Jeff Grice

Dr Grice’s work in the Therapeutics Research Centre has focussed predominantly on the area of transdermal drug absorption, studying aspects of the targeting of topically applied drugs to chosen tissues (deep or superficial) below the skin. The work examines the chemical properties of solutes applied to the skin and seeks to identify which features are significant in increasing or decreasing uptake into the body and to what extent they affect subsequent distribution into tissues, both locally and systemically.

Nanotechnology is a major theme. This ranges from formulating new nanoemulsions or nanoparticulates to act as drug carriers, to nanotoxicology, where adverse effects of materials that may be applied deliberately or inadvertently to the skin, such as nano-sunscreens, quantum dots, gold and silver nanoparticles, etc. are investigated

Underpinning much of this work is the non-invasive imaging of skin by multiphoton and confocal microscopy, which allows tracking of penetration of applied substances into the skin and analysis of metabolic and other changes that occur in the skin in response to the presence of endogenous substances.

With a background in clinical research and analytical and experimental science, Dr Grice joined the Therapeutics Research Centre in 2004. He is a co-author of 108 peer-reviewed research articles and 9 research book chapters.

As Deputy Director and Academic Manager, Dr Grice has a leading role in support of the Director, including coordination of operations with our sister centre at the University of South Australia.

Academic Staff

• Professor Mike Roberts, Director
• Dr Jeff Grice, Deputy Director & Academic Manager; Leader, Topical Delivery Group
• Dr Xin Liu, Leader, Pharmacokinetics Group
• Dr Yousuf Mohammed, Research Fellow
• Dr Xiaowen Liang, Research Fellow
• Dr Sarika Namjoshi, Research Fellow
• Dr Camilla Thompson, Research Administration Officer
• Dr Eman Abd, Research Assistant
• Dr Ahmed Mostafa, Honorary Research Fellow, Research Technologist (on secondment from University of South Australia)
• Professor Vânia Leite-Silva, Visiting Research Fellow, Brazil (February – May, 2016)

Current Students

• Mr Krishna Telaprolu
• Dr Haolu Wang
• Ms Isha Haridass (enrolled Curtin University, WA)
• Ms Christofori Nastiti (enrolled Curtin University, WA)
• Ms Shereen Yousuf (enrolled Helwan University, Egypt)

There is also a regular complement of interns from overseas Universities. In 2016, the Therapeutics Research Centre hosted 3 Pharmacy Masters students from France and 4 final-year Pharmacy students from Canada.

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.

1. Page C, Mostafa A, Saiao A, Grice JE, Roberts MS, Isbister GK. Cardiovascular Toxicity with Levetiracetam Overdose. Clinical Toxicology (Available online at http://www.tandfonline.com/doi/full/10.3109/15563650.2015.1115054) Impact factor 3.673
2. Liang X, Wang H, Grice JE, Li L, Liu X, Xu ZP, Roberts MS. Physiologically based pharmacokinetic model for long-circulating inorganic nanoparticles. Nano Letters Publication Date (Web): January 15, 2016; DOI: 10.1021/acs.nanolett.5b03854. Impact factor 13.592
3. Liang X, Wang H, Zhu Y, Cogger VC, Liu X, Xu Z, Grice JE, Roberts MS, Jeffrey E. 2016. Short- and long-term tracking of anionic ultra-small nanoparticles in kidney. ACS Nano Publication Date (Web): January 8, 2016 (Article) DOI: 10.1021/acsnano.5b05066. Impact factor 12.88
4. Abd E, Namjoshi S, Mohammed YH, Roberts MS, Grice JE. Synergistic skin penetration enhancer and nanoemulsion formulations promote the human epidermal permeation of caffeine and naproxen. J Pharm Sci. 2015 Nov 10. doi: 10.1002/jps.24699. [Epub ahead of print] Impact factor 2.59
5. Abd E, Roberts MS, Grice JE. 2016. A comparison of the penetration and permeation of caffeine into and through human epidermis after application in various vesicle formulations. Skin Pharmacol Physiol. 2016;29:24-30 (DOI:10.1159/000441040) Impact Factor 2.366
6. Sinnollareddy MG, Roberts MS, Lipman J, Peake SL, Roberts JA. (2015) Determination of Subcutaneous Interstitial Fluid Penetration and Pharmacokinetics of Fluconazole in Intensive Care Unit Patients with Sepsis Using In Vivo Microdialysis. Antimicrobial Agents and Chemotherapy 2015 Nov 23;60(2):827-32. doi: 10.1128/AAC.02461-15. Impact Factor 4.476
7. Gordon S, Daneshian M, Bouwstra J, Caloni F, Constant S, Davies DE, Dandekar G, Guzman CA, Fabian E, Haltner E, Hartung T, Hasiwa N, Hayden P, Kandarova H, Khare S, Krug HF, Kneuer C, Leist M, Lian G, Marx U, Metzger M, Ott K, Prieto P, Roberts MS, Roggen EL, Tralau T, van den Braak C, Walles H and Lehr C. (2015) Non-Animal Models of Epithelial Barriers (Skin, Intestine and Lung) in Research, Industrial Applications and Regulatory Toxicology. ALTEX 32(4), 327-378.
8. Sime F, Roberts MS, Tiong IS, Gardner J, Lehman S, Peake S, Hahn U, Warner M, Roberts JA (2015) Adequacy of high-dose cefepime regimen in febrile neutropenic patients with hematological malignancies. Antimicrobial Agents and Chemotherapy. 2015 Sep;59(9):5463-9. doi: 10.1128/AAC.00389-15. Epub 2015 Jun 29. Impact Factor 4.476
9. Michael AP, Mostafa A, Cooper JM, Grice J, Roberts MS, Isbister GK. The pharmacokinetics and pharmacodynamics of severe aldicarb toxicity after overdose. Clinical Toxicology. 2015;53(7):633-635. Impact Factor 3.122
10. Berling I, Buckley NA, Mostafa A, Downes MA, Grice JE, Roberts MS, Isbister GK. 2015. 2-methyl-4-chlorophenoxyacetic acid and bromoxynil herbicide death. Clinical Toxicology. 53(5):486-488. DOI: 10.3109/15563650.2015.1030025.  Impact factor 3.122
11. Skinner K, Mostafa A, Medley GA, Grice JE, Roberts MS, Isbister G. 2015. Isoniazid poisoning: pharmacokinetics and effect of hemodialysis in a massive ingestion. Haemodialysis International. 2015;19(4):E37-E40. DOI:10.1111/hdi.12293.  Impact Factor 1.36
12. Downes MA, Berling IL, Mostafa A, Grice J, Roberts MS, Isbister GK. Acute behavioural disturbance associated with phenibut purchased via an internet supplier. Clinical Toxicology. 2015;53(7):636-638. Impact Factor 3.122
13. Wang H, Liang X, Yousuf H. Mohammed YH, Thomas JA, Bridle KR, Thorling CA, Grice JE, Xu XP, Liu X, Crawford DHG, Roberts MS. 2015. Real-time histology in liver disease using multiphoton microscopy with fluorescence lifetime imaging. Biomedical Optics Express 6(3):780-92.  Impact Factor 3.497
14. Wang H, Thorling CA, Liang X, Bridle KR, Grice JE, Zhu Y, Crawford DHG, Xu XP, Liu X, Roberts MS. 2015. Diagnostic imaging and therapeutic application of nanoparticles targeting the liver. J Mater Chem B. 3:939.
15. Mahmood A, Liu X, Grice J, Medley G, Roberts M. 2015. Using deconvolution to understand the mechanism for variable plasma concentration-time profiles after intramuscular injection. Int J Pharm. 481(1-2):71-8.  DOI: 10.1016/j.ijpharm.2015.01.046.  Impact Factor 3.99
16. Liang X, Grice JE, Zhu Y, Liu D, Sanchez WY, Li Z, et al. 2015. Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible Quantum Dots into Sinusoidal Liver Cells. Small 11(14):1711-1720. DOI: 10.1002/smll.201402698.  Impact Factor 7.51

Dr Jeffrey Grice​

Ph: +61 7 344 38032
Email:  jeff.grice@uq.edu.au