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.
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).
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.
Optimising The Therapeutic Efficacy Of Protein-based Drugs Against Lymph-resident Diseases
Funder
National Health and Medical Research Council
Funding Amount
$348,330.00
Summary
Effective treatments for lymphatic diseases (such as HIV and lymph-metastatic cancers) are limited by the lack of drug assess towards the lymphatic sites of disease progression. Improving the access of drugs into lymph therefore has the significant potential to improve the treatment of these illnesses. We will therefore explore a novel approach to improving the lymphatic uptake and retention of protein-based drugs using a useful and widely used biologically compatible polymer.
Understanding The Mechanisms Of Nanomedicine Absorption From The Lungs And The Application Of This Knowledge To Improving The Delivery Of Chemotherapeutic Nanomedicines Towards Primary And Secondary Lung Cancers
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
The administration of chemotherapeutic 'nanomedicines' via the lungs has the capacity to improve the specific delivery of toxic anti-cancer drugs specifically towards primary and metastatic lung cancers. This project aims to evaluate how nanomedicines are absorbed from the lungs after an inhaled dose, and how they can be best developed as inhaled chemotherapeutics for the treatment of lung cancers.
Drug Targeting To Sites Of Lymph-adipose Interaction To Transform The Treatment Of Disease
Funder
National Health and Medical Research Council
Funding Amount
$515,172.00
Summary
Insulin resistance (IR) underpins the development of inadequately treated heart and metabolic diseases such as type 2 diabetes. Recently we demonstrated that high fat diets promote increased leakage of fluid from lymph vessels to abdominal fat, and that increased access of lymph fluid to fat stimulates fat expansion and changes in fat function that promote IR. This project seeks to optimise novel drug delivery strategies that target lymph and fat and more effectively treat IR.
The Mechanism Of Ccbe1 Function During Lymphangiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$502,437.00
Summary
Tumours induce the regional growth of lymphatic vessels (in a process termed lymphangiogenesis) and then spread (a process termed metastasis) via lymphatic vessels and lymph nodes. Inhibiting lymphangiogenesis can inhibit metastasis. We have identified a gene called ccbe1 that is essential for lymphangiogenesis during development. We aim to understand how this potential therapeutic target functions at the molecular level during lymphangiogenesis.
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
The Role Of Tissue Factor Pathway Inhibitor (TFPI) In The Pathogenesis Of Lymphatic Malformations
Funder
National Health and Medical Research Council
Funding Amount
$87,198.00
Summary
Lymphatic malformations or cystic hygomas are growths of abnormal blood vessels called 'lymphatic vessels'. They are present at birth, commonly affect the head and neck, and can cause lifelong problems due to growth in size and frequent infections. Surgical treatment does not offer a cure, and problems often persist lifelong. The finding that blood clots are continuously forming and breaking down in these growths may provide a clue to relieving symptoms and understanding the cause of this condit ....Lymphatic malformations or cystic hygomas are growths of abnormal blood vessels called 'lymphatic vessels'. They are present at birth, commonly affect the head and neck, and can cause lifelong problems due to growth in size and frequent infections. Surgical treatment does not offer a cure, and problems often persist lifelong. The finding that blood clots are continuously forming and breaking down in these growths may provide a clue to relieving symptoms and understanding the cause of this condition.Read moreRead less