A Biomimetic Prodrug Platform To Enable Oral Bioavailability And Target Lymphatic Disease
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
This project will allow the advance of a unique translational technology platform that provides novel drug delivery solutions. The project aims to establish the potential for a drug delivery strategy to increase the efficacy, reduce the toxicity, and transform the impact of drug therapies for a variety of conditions, including pain, hormone dysregulation, and metabolic syndrome.
Integrating Drug Delivery Principles Into Drug Design To Transform The Treatment Of Immune Disease
Funder
National Health and Medical Research Council
Funding Amount
$552,635.00
Summary
Immune system disorders (e.g. rheumatoid arthritis, transplant rejection, Crohn’s disease, multiple sclerosis) are often treated with immunosuppresant drugs. However, immunosuppressant drugs can cause significant toxicity and can lack efficacy. This proposal will show how the design of drugs used to treat immune disorders can be changed to allow drugs to be delivered specifically to their site of action (immune cells) thereby enhancing activity and reducing toxicity.
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
Snakebite is a worldwide health problem, causing some 100,000 deaths per year. We have preliminary evidence that application of nitric oxide-releasing chemical to the skin presents a novel approach to first aid treatment of venomous bites. The method has the advantage of being simple and reliable and could save lives applied by itself or as an adjunct to pressure bandaging with immobilisation (PBI).
Iron Overload Mechanisms In Dyserythropoietic Anaemias And Therapeutic Targets At The ERFE Gene Locus
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Iron overload causes organ dysfunction and morbidity for people who have red blood cell disorders such as thalassemia, or chronic transfusion requirements due to cancer or bone marrow failure. The manner in which a principal controlling compound, erythroferrone, influences iron metabolism is undefined. Our project will use molecular approaches to determine how the erythroferrone gene is involved in causing iron overload in red cell disorders and potentially open better management pathways.