Despite the acknowledged limitations of ophthalmic medication by means of topical guttae therapy, including toxicity, inefficiency and poor compliance, there has been no success in developing a true alternative suitable for a wide range of conditions. The availability of a simple, safe efficacious means of prolonged topical ophthalmic drug delivery would alter the practice of ophthalmology worldwide, with reduced morbidity, improved compliance and direct and indirect health savings. Poor patient ....Despite the acknowledged limitations of ophthalmic medication by means of topical guttae therapy, including toxicity, inefficiency and poor compliance, there has been no success in developing a true alternative suitable for a wide range of conditions. The availability of a simple, safe efficacious means of prolonged topical ophthalmic drug delivery would alter the practice of ophthalmology worldwide, with reduced morbidity, improved compliance and direct and indirect health savings. Poor patient compliance with topical guttae therapy is increasingly recognised as a source of significant morbidity. The occurrence of such a breakthrough in Australia would result in Australia benefiting from the boost to a medical biomaterial industry based here, with a large export market for a high value-m3 product. During the next phase of research for this project, over 1 year, we aim to do the following: Phase I: Manufacture a range of prototype devices, with variations in sponge and surface composition and evaluate these devices using a Sintech mechanical tester for elasticity and strength and by light and environmental scanning electron microscopy for structure and porosity. The liquid loading capacity will also be measured for each variant. Phase II: Using both hydrophilic and lipophilic models, drug loading and release kinetics will be assessed in vitro in a continuous flow system, with drug concentrations being measured by UV-Vis and HPLC. Drug stability within the devices will also be assessed. Phase III: Having determined the optimum sponge formulation and release kinetics in vitro, a pilot study will be undertaken to assess drug release in an animal model. Loaded devices will be placed within the inferior fornix the rabbits for specified periods from 0.5 to 96 hours, then removed so that drug levels remaining in the device can be assessed. After a 2 week flushing period, the experiments will be repeated but with animals being sacrificed at the end of the wearing period so that device levels in intraocular tissues and fluids, as well as remaining in the devices, can be determined at these times, with appropriate controls (‘blank’ devices and guttae therapy). This study will also fulfil the requirements for new device tolerance testing as specified by Regulatory authorities, as animals will be monitored for signs of irritation and histological studies will allow any evidence of inflammation to be identified. These studies do not allow evaluation of the device in a model diseased eye, nor attempt to establish drug loading levels required for human subjects, as there are differences in drug transport across the ocular surfaces of rabbits and humans, but will allow sufficient proof-of-principle for further development to occur.Read moreRead less
Non-invasive Measurement And Imaging Of Hepatic Iron Concentrations Using Nuclear Magnetic Resonance
Funder
National Health and Medical Research Council
Funding Amount
$341,210.00
Summary
Iron overload diseases such as genetic haemochromatosis and thalassaemia affect up to 0.5% of the world's population. These diseases result in deposition of dangerously high concentrations of iron in tissues of the body. Organs such as the liver and heart are at particular risk of being damaged. In order to manage a patient's condition optimally, a knowledge of their tissue iron concentrations is required. Currently the most direct and reliable way of achieving this is to remove a small sample o ....Iron overload diseases such as genetic haemochromatosis and thalassaemia affect up to 0.5% of the world's population. These diseases result in deposition of dangerously high concentrations of iron in tissues of the body. Organs such as the liver and heart are at particular risk of being damaged. In order to manage a patient's condition optimally, a knowledge of their tissue iron concentrations is required. Currently the most direct and reliable way of achieving this is to remove a small sample of the patient's liver for chemical analysis. Apart from the fact that the procedure is unpleasant and carries some risk, the measurement made by this method has some uncertainty because the liver iron concentration can vary significantly from place to place within the liver. The aim of this project is to test the validity of a new non-invasive method of measuring and imaging the liver iron concentrations of a patient. In addition, the potential to use the new technology for detecting and imaging liver cirrhosis in iron overloaded patients will be evaluated. If successful, the project may lead to a more accurate method of measuring tissue iron concentrations and eliminate the need for invasive procedures.Read moreRead less
Novel System For Non-Invasive Delivery Of Drugs To The Interior Of The Eye
Funder
National Health and Medical Research Council
Funding Amount
$200,213.00
Summary
Age-related macular degeneration (AMD) is the leading cause of visual loss for adults in the developed world. Treatment is now by needle injection into the back of the eye, which is painful for the patient and is costly for the health-care system. Seagull Technology Pty Ltd has developed a non-invasive device for treating the back of the eye without the need for a needle injection. This project will test the new device in animals and then move to a first safety study for human AMD patients.
Toxicological And Pre-clinical Assessment Of The Anti-cancer Compound Bp4eT
Funder
National Health and Medical Research Council
Funding Amount
$198,900.00
Summary
Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Development Grant, we will perform toxicological studies to enable clinical trials of our most promising novel iron chelator to commence.