Drugs are applied to the skin for the treatment of a wide range of conditions including both local (inflammation, pain, eczema, psoriasis) and systemic (angina, nicotine withdrawl, hormone replacement therapy) therapies. Unwanted skin absorption also occurs following exposure to environmental and occupational chemicals, including those applied deliberately to the skin such as insectisides, sunscreens and cosmetics. This study seeks to examine the relationship between the chemical structure of ag ....Drugs are applied to the skin for the treatment of a wide range of conditions including both local (inflammation, pain, eczema, psoriasis) and systemic (angina, nicotine withdrawl, hormone replacement therapy) therapies. Unwanted skin absorption also occurs following exposure to environmental and occupational chemicals, including those applied deliberately to the skin such as insectisides, sunscreens and cosmetics. This study seeks to examine the relationship between the chemical structure of agents, the types of formulations in which they are applied and their penetration into the various layers of the skin and underlying tissues. We intend to further our research into important areas relating to the ability to predict the likely behaviour of a solute which comes into contact with the skin from the aspect of optimising both topical drug delivery systems and risk assessment procedures. We will also be examining techniques of facilitating drug transport through the skin using (i) the knowledge gained of the mechanisms by which vehicles act on the skin, (ii) the synthesis of ester and amide lipophilic prodrugs and (iii) physical techniques such as iontophoresis, whereby small electrical currents are applied to charged drug species on the outside of the skin.Read moreRead less
Biological Membrane Transporters: Delivery Of An Oligonucleotide Inhibitor Of Vascular Endothelial Growth Factor (VEGF)
Funder
National Health and Medical Research Council
Funding Amount
$99,750.00
Summary
Choroidal neovascularisation, which is the most severe form of Age Related Macular Degeneration, is the major cause of blindness in the developed world. Gene therapy could be a cure for this disease if the problems associated with the delivery of DNA could be addressed. Our project involves a highly novel strategy for gene delivery involving ion pair formation of lipophilic dendrimers (tree-like compounds with positive charges on the surface). We will develop new DNA-dendrimer complexes and test ....Choroidal neovascularisation, which is the most severe form of Age Related Macular Degeneration, is the major cause of blindness in the developed world. Gene therapy could be a cure for this disease if the problems associated with the delivery of DNA could be addressed. Our project involves a highly novel strategy for gene delivery involving ion pair formation of lipophilic dendrimers (tree-like compounds with positive charges on the surface). We will develop new DNA-dendrimer complexes and test them in a well established animal model for neovascularisation. Successful completion of this project might offer a potential therapy for choroidal neovascularisation, with a good chance of entering into human clinical trials.Read moreRead less
Development Of A Generic Strategy For The Stabilisation Of Peptide-based Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$443,196.00
Summary
There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides the ....There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides therapeutically promising peptides and proteins the ability to resist the body s natural degradation pathways so they are able to reach their biological target. To develop this strategy we will use the recently discovered peptide hepcidin as a model system. Hepcidin is the major iron-regulatory hormone in the human body and incorrect levels of this hormone result in either iron overload (haemochromatosis), when there is not enough hepcidin produced by the body, or anemia of inflammation when there is too much hepcidin. The development of hepcidin-based therapeutic agents to treat these conditions has the potential to have significant impact as it has been estimated that up to 1 in 300 Australians are affected by haemochromatosis during their lifetimes. Unfortunately, unmodified peptides, like hepcidin, are of limited therapeutic value due to their poor stability within the human body. This research proposal describes the development of stabilised hepcidin analogues with the potential of being useful drug leads for the treatment of haemochromatosis.Read moreRead less
Drugs are applied to the skin for the treatment of a wide range of conditions, including both local (eg. inflammation, muscle pain, eczema, psoriasis and other dermatological conditions) and systemic (eg. angina, hormone replacement, nicotine withdrawal) therapies. Advances in molecular biology technology has also led to the development of a range of large molecular weight peptide and protein based therapeutic agents for which transdermal delivery offers the most cost-effective and practical sol ....Drugs are applied to the skin for the treatment of a wide range of conditions, including both local (eg. inflammation, muscle pain, eczema, psoriasis and other dermatological conditions) and systemic (eg. angina, hormone replacement, nicotine withdrawal) therapies. Advances in molecular biology technology has also led to the development of a range of large molecular weight peptide and protein based therapeutic agents for which transdermal delivery offers the most cost-effective and practical solution if appropriate delivery systems can be identified. In addition, unwanted skin absorption also occurs following exposure to environmental occupational chemicals, and those applied deliberately to the skin such as insecticides, sunscreens and cosmetics. This study continues our work in seeking to define the relationship between the chemical structure of agents, the types of formulations and solvents in which they are applied or come into contact with the skin and their penetration, distribution and retention in the various layers of the skin and underlying tissues. Of great significance to both the pharmaceutical industry and risk assessment regulatory bodies will be the further development of our work into important areas relating to the ability to predict the likely behaviour of a solute following contact with the skin from the aspect of both optimising drug delivery systems and the accuracy of risk assessment procedures. We will also be continuing our work examining techniques to facilitate drug transport through the skin using physical techniques such as iontophoresis and the design of formulations to specifically target larger pores in the skin such as hair follicles as a means of improving delivery rates and increasing the range of solutes, particularly those of large molecular weight, likely to be considered as potential drug candidates.Read moreRead less
Rationally Designed Targeted Core Shell Nano-Construct For Improved Anticancer Effects And Enhanced Bone Fracture Healing In Breast Cancers Metastasised To Bone
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
The main objective of the project is to develop and evaluate a single therapeutic system comprising chemotherapeutic as well as bone fracture healing agent, which will overcome the drawbacks of the conventional treatment for skeletal bone metastasised breast cancers. This therapeutic system will specifically accumulates in the tumour sites and release the chemotherapeutic enabling anticancer effects, followed by the slow release of bone fracture healing agent results in healing of fractures.
Development Of Drug-loaded Antibody-targeted Nanoparticles To Kill Colorectal Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$513,146.00
Summary
COLORECTAL CANCER (CRC) is the most common cancer in the Western world. In Australia, the five-year survival rate after surgical resection of the primary lesion is 55%, and for patients with advanced disease the five-year survival rate is less than 10%. Colorectal cancer is relatively resistant to radiotherapy and chemotherapy and therefore there is great emphasis on identifying alternative modes of treatment. One approach that is attracting considerable attention is IMMUNOTHERAPY. In particular ....COLORECTAL CANCER (CRC) is the most common cancer in the Western world. In Australia, the five-year survival rate after surgical resection of the primary lesion is 55%, and for patients with advanced disease the five-year survival rate is less than 10%. Colorectal cancer is relatively resistant to radiotherapy and chemotherapy and therefore there is great emphasis on identifying alternative modes of treatment. One approach that is attracting considerable attention is IMMUNOTHERAPY. In particular, the A33 ANTIBODY system appears to have the potential to target colorectal cancer cells and achieve therapeutic outcomes. The A33 system has been well characterised in both a clinical and laboratory setting over the last few years and recent clinical trials with humanised versions of the A33 antibody have demonstrated rapid localisation and accumulation of radiolabelled A33 to colorectal cancer lesions. The application of NANOTECHNOLOGY to biological systems is likely to transform the way we treat a variety of diseases over the course of the next decade. Nanosized drug delivery vehicles have the potential to revolutionise the treatment of a number of diseases, cancer in particular. Hollow capsules can be synthesised with a drug sequestered inside the capsule, where the capsule wall performs a dual role of protecting the body from potentially harmful side effects of the drug, as well as protecting the drug from being degraded by the body. We plan to use these nanosized drug carriers, functionalised with the A33 antibody, to deliver chemotherapy agents directly to the colorectal cancer cells. We have recently demonstrated that in vitro, nanocapsules functionalised with the A33 antibody specifically bind to CRC cells, and once bound, the capsules are internalised. In this proposal we will test the ability of these particles to kill CRC cells in mice harbouring human tumours.Read moreRead less
Manufacture And Testing Of Next Generation Orthopaedic Implants Harnessing Periosteum's Regenerative Power
Funder
National Health and Medical Research Council
Funding Amount
$508,314.00
Summary
Tissue defects, e.g. due to trauma or tumor removal, are too large to heal without reconstructive surgery. Complications associated with defect repair may diminish the patient's quality of life and productivity, posing significant medical and psychosocial costs. Here we propose a plan to define technical specifications for next generation, "smart" orthopaedic implants that deliver cells and the signals they need to build new tissue using nature's paradigms.
A New Approach For The Treatment Of COPD And Lung Cancer Using Inhaled Retrometabolic HSP90 Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$638,310.00
Summary
The inflammatory lung disease Chronic Obstructive Pulmonary Disease (COPD) is a major disease burden in Australia with over 1 million sufferers and being the fourth biggest killer. Lung cancer is one of the most difficult cancers to treat with 5-year survival rates being below 20%. There is a pressing need for new therapies to treat these diseases and this project will develop new drugs designed to inhibit an underlying mechanism present in both diseases, with minimal side-effects.
Lipoceramic Technologies: A Solution To Low And Variable Bioavailability Of Poorly Soluble Anti-inflammatory Drugs
Funder
National Health and Medical Research Council
Funding Amount
$200,600.00
Summary
A novel oral drug delivery platform will be developed that improves the absorption of poorly soluble drugs from the GI tract, leads to improved clinical outcomes and has significant commercial value. This development will be based on the combination of formulation, in vitro analysis and in vivo animal model studies. An advanced prototype formulation will be established for celecoxib (a non-steroidal anti-inflamatory drug) that will be suitable for human phase 1 clinical trials.
Non-invasive Therapy For Keratoconus – Ultrasound Enhanced Delivery Of Riboflavin To Cornea For Transepithelial Corneal Collagen Crosslinking
Funder
National Health and Medical Research Council
Funding Amount
$600,658.00
Summary
Keratoconus is a degenerative eye disease which causes corneal thinning. The disease causes visual distortions & loss of vision, and is commonly treated with Corneal Cross-Linking. This involves scraping off the outer protective layer of the cornea so that treatment can be applied. This is painful for patients and carries many risks. This grant assists in the development of a device that is able to deliver the reagent in a painless, non-invasive, effective and safe way.