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.
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
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.
Phosphonated Calixarenes For The Targeted Intracellular Delivery Of Anticancer Agents
Funder
National Health and Medical Research Council
Funding Amount
$322,267.00
Summary
Many anticancer drugs have severe side effects due to their potency and non-specificity of action. To improve the treatment outcome for thousands of cancer patients, we aim to engineer calixarene-based nanocarriers that bypass normal tissues to selectively deposit drugs and imaging agents into tumour cells. Such delivery systems will optimize the performance of a host of anticancer agents that act within cells, and enable drug treatment and monitoring to be simultaneously realised.
Structure And Function Of Antimicrobial Therapies And Their Interaction With Upper Respiratory Biofilms
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Bacterial infections of the upper respiratory tract are a major public health problem affecting millions of Australians. Commonly prescribed antibiotics are often not able to eradicate all bacteria as the bacteria often reside in a protective, self-produced gel-like matrix known as biofilm. This Fellowship aims to unravel the interaction of modern anti-infective therapeutics with the biofilm for the development of the next generation of safe and efficacious anti-biofilm strategies.
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
Influence Of Skin Cancer On Topical Elongate Microparticle Drug Delivery
Funder
National Health and Medical Research Council
Funding Amount
$560,589.00
Summary
This project builds on a novel cutaneous delivery method using ‘rod-shaped’ microparticles we developed in the Dermatology Research Centre. Microparticle administration results in multiple punctures of the skin’s tough outer layers, increasing permeability. Furthermore, microparticle administration results in a uniform and continuous drug delivery profile within the treatment area, which is an important attribute for the treatment of skin diseases.
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
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.