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.
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
Novel Cellular Trafficking Mechanisms For The Drug Influx Transporter, Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in indivi ....Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in individuals.Read moreRead less
A Nanostructured Drug Delivery Approach For Improved Colorectal Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$560,072.00
Summary
Based on nanotechnology a new medicine will be developed for chemotherapy drugs. Drugs that are currently only delivered by injection will be able to be taken as an orally dosed tablet. A novel therapy for colorectal cancer will be advanced with potential improved clinical outcomes and reduced side-effects, e.g. nausea and diarrhoea. Cancer patients will no longer need to visit the hospital for injection therapy and therefore reducing the burden on the health service.
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.
Recognition Of Macromolecular Complexes By Cell Surface Receptors: A Novel Mechanism Of Lipid And Drug Absorption
Funder
National Health and Medical Research Council
Funding Amount
$398,156.00
Summary
A clear understanding of the mechanisms by which orally ingested materials are absorbed from the gastrointestinal tract is critical in areas such as nutrition, drug development and toxicology. The current project aims to evaluate the role of specific receptor types in the intestine in the absorption of both dietary lipids and drug molecules, with a view to providing a means to better regulate lipid absorption and to more effectively facilitate the design of improved drug delivery systems.
Novel System For Non-Invasive Delivery Of Drugs To The Interior Of The Eye
Funder
National Health and Medical Research Council
Funding Amount
$200,213.00
Summary
Age-related macular degeneration (AMD) is the leading cause of visual loss for adults in the developed world. Treatment is now by needle injection into the back of the eye, which is painful for the patient and is costly for the health-care system. Seagull Technology Pty Ltd has developed a non-invasive device for treating the back of the eye without the need for a needle injection. This project will test the new device in animals and then move to a first safety study for human AMD patients.