A Novel Tumour-targeting Nanoliposome Drug Delivery System For The Treatment Of Malignant Gliomas
Funder
National Health and Medical Research Council
Funding Amount
$445,097.00
Summary
Most patients with malignant brain tumours die within a year after diagnosis due to the difficulty in effectively delivering drugs to the tumour cells. We aim to develop a safe and novel drug delivery system to effectively deliver anticancer drugs and novel anticancer agents to brain tumour cells that remain in normal brain after surgery. The success of this project will bring us a step forward in our efforts to significantly improve the survival rate and quality of life of such patients.
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
Antibiotic Loading Of Bone Allografts For The Prevention Of Peri-operative Infection
Funder
National Health and Medical Research Council
Funding Amount
$300,847.00
Summary
Bone is the second most often transplanted tissue after blood, with thousands of grafts done every year in Australia. Allograft bone (taken from another person) is used to replace bone removed due to cancer, but is prone to infection. Infected grafts must be removed, and can lead to amputation. We are developing a process to put antibiotics into allograft bone, to prevent infections from taking hold. Reducing infections can increase the success of limb salvage surgery for cancer patients.
MPM Non-invasive Imaging Of Biological Interactions Following Drug Delivery With Micro-nanoprojection Patches.
Funder
National Health and Medical Research Council
Funding Amount
$403,612.00
Summary
The overarching aim of my research is to develop and evaluate effective, practical and reproducible physical methods for delivering genes and drugs to specific immunologically-sensitive cells in the skin to ultimately treat and vaccinate against human diseases. I recently patented a method using arrays of nano-scale projections on a patch to accurately, efficiently and safely deliver biomolecules not just to specific skin cells, but also to organelles within them. Conceptually, the delivery devi ....The overarching aim of my research is to develop and evaluate effective, practical and reproducible physical methods for delivering genes and drugs to specific immunologically-sensitive cells in the skin to ultimately treat and vaccinate against human diseases. I recently patented a method using arrays of nano-scale projections on a patch to accurately, efficiently and safely deliver biomolecules not just to specific skin cells, but also to organelles within them. Conceptually, the delivery device is a set of microscopic nanoneedles coated with drug substance and applied to the skin as a small patch. The device is practical, needle-free and pain-free. The aim of this current project is to use the micro-nanoprojection array patches-configured to uniquely deliver biomolecules to cells within given strata-to find: 1) what delivery sites of antigen-expression plasmid- toll like receptor (TLR) agonist lead to strong humoral immune responses in the intact animal. 2) whether delivery of different TLR agonists have different effects on the maturation and migration of the different professional antigen presenting cells (APCs) in the skin, as visualised locally by Multi-Photon Microscopy (MPM). 3) whether differences in APC maturation and migration are associated with different systemic antibody responses. We will identify optimal delivery sites of drugs-vaccines to the skin (layer, cells targeted, duration of delivery) with MPM for desired systemic immune responses. This will have important contributions towards improving immunotherapeutics of major diseases via skin targeting with micro-nanoprojection array patch technologies (and other methods).Read moreRead less
Antibody-directed Delivery Of Anti-restenotic Agents Using Inorganic Nanoparticles
Funder
National Health and Medical Research Council
Funding Amount
$327,151.00
Summary
Arteries that have been surgically treated to remove fatty lesions that block blood flow frequently become re-blocked (restenosed), and drugs to prevent this re-blockage often have bad side-effects. We propose to prevent these complications by target-delivering the drugs directly and only to the required site using a single injection at the time of surgery. This will limit systemic side-effects, treatment costs and incidence of reblocking and bleeding complications.
Targeting Alpha-conotoxin MII To Inhibit Neuronal Nicotinic Acetylcholine Alpha3beta2 Receptors Of The CNS
Funder
National Health and Medical Research Council
Funding Amount
$218,334.00
Summary
Nicotinic acetylcholine receptors (nAChRs) play a central role in nerve signal transmission, neurite growth and development and are the representative model of the ligand-gated ion channel superfamily. Recent studies, including those from Dr Lewis' and A-Prof Alewood's laboratories, have identified alpha-conotoxin peptides which can discriminate among the different nAChRs, apparently by binding to the specific interfaces formed by different subunit combinations. Thus alpha-conotoxins are unique ....Nicotinic acetylcholine receptors (nAChRs) play a central role in nerve signal transmission, neurite growth and development and are the representative model of the ligand-gated ion channel superfamily. Recent studies, including those from Dr Lewis' and A-Prof Alewood's laboratories, have identified alpha-conotoxin peptides which can discriminate among the different nAChRs, apparently by binding to the specific interfaces formed by different subunit combinations. Thus alpha-conotoxins are unique tools with which to identify and determine the physiological role, played by the different native neuronal nAChRs. Moreover, they are unusually stable peptides and can withstand enzyme and acid treatment. These findings have encouraged us to pursue the viability of alpha-conotoxin MII as a new and selective antagonist for the neuronal nictotinic receptor alpha3 beta2 which is involved in nicotine addiction. The challenge and major goal of this project is to deliver alpha-conotoxin MII efficiently into the brain. A-Prof Toth has developed a novel drug-delivery system for the oral administration of drugs and peptides, which in their unmodified form are poorly absorbed or biologically unstable. In this project alpha-conotoxin MII will be combined with a specifically designed lipopolysaccharide delivery system . The delivery system can be specifically tailored to transport a wide variety of peptides through the different biological barriers. The peptides can be conjugated to the delivery system in such a way as to release the peptide after it has been absorbed (prodrug), or to form a biologically stable and active novel molecule. The outcomes of this work will include the first delivery system of nicotinic antagonists to the brain and new knowledge concerning the importance of the neuronal nictotinic receptor alpha3 beta2 in nicotine addiction.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
Nanopatch Immunisation Against Pandemic Influenza: Improved Immune Responses At A Reduced Dose.
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Development of a new way to vaccinate against influenza that will make standard vaccines 100 times more potent than conventional syringe injection. The Nanopatch is made from a silicon wafer, bristling with micro-nanoscale spikes. It painlessly deposits vaccine under the skin surface. Experiments in mice show that even a small vaccine payload delivered to the skin generates good immune responses. The Nanopatch vaccination system is expected to be ready for clinical trials within a few years.
Nanoparticle Based Neurotrophin Delivery To Promote Directed Neurite Growth And Auditory Nerve Rescue Following Deafness
Funder
National Health and Medical Research Council
Funding Amount
$506,724.00
Summary
The cochlear implant provides hearing information to the severe-profoundly deaf by electrically stimulating the auditory nerves of the inner ear. Deafness causes these auditory nerves to gradually degenerate leaving fewer nerves for the cochlear implant to stimulate. We propose to reverse this neural degeneration by delivering therapeutic drugs to the inner ear using tiny nanoparticles. This novel technology is expected to have application in other areas of neural degenerative disease.