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
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.
Bisphosphonate Use, Oral Flora, Saliva, Gingival Crevicular Fluid And Bone Markers In Patients With Jaw Osteonecrosis
Funder
National Health and Medical Research Council
Funding Amount
$121,751.00
Summary
Bisphosphonates are used in patients with bones that break easily due to conditions such as osteoporosis. Recent research suggests a possible association between these drugs and jaw bone breakdown called jaw osteonecrosis - a devastating condition with no current effective treatment. It is unclear why this condition affects only jaw bones. This study seeks to investigate if bacteria in the mouth, gum disease and saliva are involved in jaw osteonecrosis, which can then help to improve management.
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
The CCRE for Oral Health will focus on the prevention and treatment of oral diseases and disorders and their clinical consequences. Research will emphasise three areas of clinical care that are critical to the management of oral health, systemic health and general well-being: 1.Primary prevention to prevent disease onset 2. Diagnosis and risk prediction for oral conditions 3. Clinical intervention
Caries Initiation Across Childhood To Adulthood By Exposure To Water Fluoridation
Funder
National Health and Medical Research Council
Funding Amount
$198,297.00
Summary
This research program is expected to contribute to filling significant gaps in the understanding of factors determining the oral health of Australian children and young adults. The purpose of the project is to develop a better understanding of the outcome of long-term exposure to fluoridated water among young adults.
The South Australian Dental Longitudinal Study has been the first comprehensive dental longitudinal study of older adults to be conducted in Australia. Participants were aged 60+ years at the 1991 baseline data collection, and were a random sample of community-dwelling older adults in urban Adelaide and rural Mount Gambier. The 11-year follow-up data collection will build upon the previous study findings to provide important and new information about the onset and progression of oral diseases in ....The South Australian Dental Longitudinal Study has been the first comprehensive dental longitudinal study of older adults to be conducted in Australia. Participants were aged 60+ years at the 1991 baseline data collection, and were a random sample of community-dwelling older adults in urban Adelaide and rural Mount Gambier. The 11-year follow-up data collection will build upon the previous study findings to provide important and new information about the onset and progression of oral diseases in older Australians. It will also assist with the identification of general health and other characteristics (socio-demographic, medical, functional, cognitive, nutritional, swallowing, dental history, oral hygiene care, financial, social support and oral disorder social impact characteristics) that are associated with oral diseases in various groups of older adults. Groups of older adults within the study include those who are healthy and living in the community, those who are frail and use support services, and those who have moved into residential care. This information will assist both private and public health sectors, dental professionals and other health professionals with the identification of those older adults who are at high risk for developing oral diseases, such as those with dementia, those with physical disabilities, and those living in residential care. This 11-year data collection will be one of only 4 similar international studies currently being conducted, and will provide important comparison data for future studies of older Australians.Read moreRead less