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Enhanced drug delivery using nanoparticulate dendrimer vectors. Many drug candidates fail during development because of low and variable absorption after oral administration. This project seeks to investigate the utility of specialised nanometer-sized macromolecules (dendrimers), to facilitate the improved delivery of drug molecules where low aqueous solubility is the principle limitation to drug absorption and will also be explored as vectors to specifically target drugs to intestinal lymphoid ....Enhanced drug delivery using nanoparticulate dendrimer vectors. Many drug candidates fail during development because of low and variable absorption after oral administration. This project seeks to investigate the utility of specialised nanometer-sized macromolecules (dendrimers), to facilitate the improved delivery of drug molecules where low aqueous solubility is the principle limitation to drug absorption and will also be explored as vectors to specifically target drugs to intestinal lymphoid (immune) tissue. This project will link the drug delivery expertise of Monash University with the experience in dendrimer design of the Australian biotechnology company Starpharma to provide concrete delivery solutions for the rapidly expanding biotechnology industry in Australia.Read moreRead less
Rational Design of Pegylated Dendrimer Nanostructures for Site Specific Drug Delivery. This project will provide technological advances with significant benefits in terms of improved drug treatment, and therefore health outcomes for Australia. The project builds on areas of research strength in Australia (nanotechnology and biotechnology/biomaterials) and will add considerably to the expanding Australian expertise-base in dendrimer technology (in which it is a world leader). The interdisciplinar ....Rational Design of Pegylated Dendrimer Nanostructures for Site Specific Drug Delivery. This project will provide technological advances with significant benefits in terms of improved drug treatment, and therefore health outcomes for Australia. The project builds on areas of research strength in Australia (nanotechnology and biotechnology/biomaterials) and will add considerably to the expanding Australian expertise-base in dendrimer technology (in which it is a world leader). The interdisciplinary nature of this project will also result in a unique training program for the researchers included in this grant. Such experience is in great demand, particularly in Australia where the burgeoning start-up discovery industry is critically short of personnel with skills in drug delivery.Read moreRead less
Therapeutic approaches to treat human immunodeficiency virus infection: development of HIV-1 integrase inhibitors. This project aims to assist the development of new anti-HIV drugs, which would benefit the 15000 Australians and over 40 million people worldwide who are currently infected with this terrible disease. The project will utilise state of the art technologies - including the Australian Synchrotron when it is commissioned in 2007 - to identify and synthesise compounds as new leads for th ....Therapeutic approaches to treat human immunodeficiency virus infection: development of HIV-1 integrase inhibitors. This project aims to assist the development of new anti-HIV drugs, which would benefit the 15000 Australians and over 40 million people worldwide who are currently infected with this terrible disease. The project will utilise state of the art technologies - including the Australian Synchrotron when it is commissioned in 2007 - to identify and synthesise compounds as new leads for the treatment of HIV.Read moreRead less
Targeting virulence of Pseudomonas aeruginosa by inhibiting oxidative protein folding. Our research will lead to the development of compounds with a novel anti-virulence/antibacterial mode of action for further drug development.
Mechanisms of enhancement of absorption of poorly water-soluble drugs from the gastrointestinal tract mediated by lipids, surfactants and polymers. This project will provide technological advances with significant benefits in terms of improved drug treatment, and therefore health outcomes for Australia. The projects builds on internationally recognised research strengths at Monash University in lipid-based drug delivery, and connects Monash and Australia with applied research in the multination ....Mechanisms of enhancement of absorption of poorly water-soluble drugs from the gastrointestinal tract mediated by lipids, surfactants and polymers. This project will provide technological advances with significant benefits in terms of improved drug treatment, and therefore health outcomes for Australia. The projects builds on internationally recognised research strengths at Monash University in lipid-based drug delivery, and connects Monash and Australia with applied research in the multinational pharmaceutical industry. This will enhance the standing of Australian biomedical research in the pharmaceutical world and directly facilitate a partnership between Monash and Capsugel in commercialisation of the outcomes of the project. The project will also train Australian scientists in skills that are in great demand in the developing pharmaceutical industry in Australia.Read moreRead less
DsbA: A target for the design of drug candidates as selective inhibitors of oxidative protein folding in Gram negative bacteria. There is a clear need for development of novel antibiotics which are capable of treating the increasingly prevalent strains of pathogenic bacteria that are resistant to currently available drugs. In this proposal we will design novel inhibitors of bacterial enzymes that are required for the correct folding of a variety of proteins and test the effects of these molecule ....DsbA: A target for the design of drug candidates as selective inhibitors of oxidative protein folding in Gram negative bacteria. There is a clear need for development of novel antibiotics which are capable of treating the increasingly prevalent strains of pathogenic bacteria that are resistant to currently available drugs. In this proposal we will design novel inhibitors of bacterial enzymes that are required for the correct folding of a variety of proteins and test the effects of these molecules on enzyme activity, bacterial growth and antibiotic resistance. Specific inhibitors of these enzymes constitute a novel strategy for the treatment of bacteria that have developed resistance to existing antimicrobial drugs.
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Functional characterisation of neurons derived from embryonic stem cells and NS cells. The ability to obtain specific neurons from NS cells will revolutionise the study of nerve function, will allow the establishment of much-improved models for discovery of new drugs, and will define how enriched populations of neural cells can be obtained for applications in treatment of neurodegenerative diseases. The project will provide vital data for the emerging biotechnology industry associated will appl ....Functional characterisation of neurons derived from embryonic stem cells and NS cells. The ability to obtain specific neurons from NS cells will revolutionise the study of nerve function, will allow the establishment of much-improved models for discovery of new drugs, and will define how enriched populations of neural cells can be obtained for applications in treatment of neurodegenerative diseases. The project will provide vital data for the emerging biotechnology industry associated will applications of stem cell biology, and will stimulate clinical researchers to investigate the therapeutic potential of cell derived from NS cells.Read moreRead less
Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules. Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hya ....Perturbation of the extracellular architecture to promote the absorption and lymphatic transport of biological macromolecules. Macromolecules therapeutics such as proteins, antibodies or polymer conjugates pose a number of pharmaceutical challenges. Where the dose is high, drainage of that dose from a subcutaneous injection site into the circulation, poses a particular problem. Here the project aims to explore how recombinant hyaluronidase, an enzyme that breaks down a structural component (hyaluronan) of the interstitum, can be used promote absorption into the draining blood and lymph capillaries. The project aims to also explore the downstream effects of hyaluronidase on lymph nodes and evaluate whether the enzyme is able to temporarily disrupt the lymph node structure and promote drug penetration into the lymph node mass. This has significant potential for improved drug targeting.Read moreRead less
Synergising nanoemulsion and lipid biomimetic design for advanced delivery. This project aims to identify the critical design characteristics of lipid formulations of lipid-modified probes or drugs (lipid biomimetics) that together promote integration into lipid absorption pathways and target the lymphatic system that drains the small intestine. This has significant potential since the intestinal lymphatic system is a key immune tissue, the site of immune response to autoantigens and antigens de ....Synergising nanoemulsion and lipid biomimetic design for advanced delivery. This project aims to identify the critical design characteristics of lipid formulations of lipid-modified probes or drugs (lipid biomimetics) that together promote integration into lipid absorption pathways and target the lymphatic system that drains the small intestine. This has significant potential since the intestinal lymphatic system is a key immune tissue, the site of immune response to autoantigens and antigens derived from food and the microbiome. The project will deliver a design roadmap of the required characteristics for lymphatic targeting, and in particular, will identify novel lipid nanoemulsions that work synergistically with lipid biomimetics to enhance lymphatic imaging and delivery applications.Read moreRead less
Controlling the spatial distribution of targeting ligands on dendrimer surfaces as a means of dictating cellular recognition and fate. This project seeks to develop next generation targeted drug delivery systems that 'home' to specific target cells, including cancers. Targeted delivery systems have the potential to revolutionise therapy by providing bespoke drug distribution patterns that are tailored to specific diseases and result in enhanced activity and reduced toxicity.