Drugs are applied to the skin for the treatment of a wide range of conditions, including both local (eg. inflammation, muscle pain, eczema, psoriasis and other dermatological conditions) and systemic (eg. angina, hormone replacement, nicotine withdrawal) therapies. Advances in molecular biology technology has also led to the development of a range of large molecular weight peptide and protein based therapeutic agents for which transdermal delivery offers the most cost-effective and practical sol ....Drugs are applied to the skin for the treatment of a wide range of conditions, including both local (eg. inflammation, muscle pain, eczema, psoriasis and other dermatological conditions) and systemic (eg. angina, hormone replacement, nicotine withdrawal) therapies. Advances in molecular biology technology has also led to the development of a range of large molecular weight peptide and protein based therapeutic agents for which transdermal delivery offers the most cost-effective and practical solution if appropriate delivery systems can be identified. In addition, unwanted skin absorption also occurs following exposure to environmental occupational chemicals, and those applied deliberately to the skin such as insecticides, sunscreens and cosmetics. This study continues our work in seeking to define the relationship between the chemical structure of agents, the types of formulations and solvents in which they are applied or come into contact with the skin and their penetration, distribution and retention in the various layers of the skin and underlying tissues. Of great significance to both the pharmaceutical industry and risk assessment regulatory bodies will be the further development of our work into important areas relating to the ability to predict the likely behaviour of a solute following contact with the skin from the aspect of both optimising drug delivery systems and the accuracy of risk assessment procedures. We will also be continuing our work examining techniques to facilitate drug transport through the skin using physical techniques such as iontophoresis and the design of formulations to specifically target larger pores in the skin such as hair follicles as a means of improving delivery rates and increasing the range of solutes, particularly those of large molecular weight, likely to be considered as potential drug candidates.Read moreRead less
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
Structure-based Design Of Inhibitors Of Oxidative Protein Folding In Enterobacteriaceae.
Funder
National Health and Medical Research Council
Funding Amount
$523,540.00
Summary
Antibiotic resistance represents a major public health problem. For gram-negative bacteria in particular, the situation is increasingly bleak, with the accumulation of resistance to existing drugs and few if any new drugs in the pipeline. We are using structure-based drug design to develop novel strategies for the treatment of gram-negative bacterial infections.
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
Exploitation Of Bacterial Transcription Initiation As A Target For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
Antibiotic resistant infections from 'superbugs' are a major health problem. We will exploit information we have gathered on the machinery that copies genetic information into a message to discover chemical compounds that can be used for the development of new antibiotics with a novel mechanism of action.
Plasmodium Falciparum Neutral Aminopeptidases: Structure-function Analysis For The Discovery Of Anti-malarial Drugs.
Funder
National Health and Medical Research Council
Funding Amount
$634,027.00
Summary
Malaria is the world's most prevalent parasitic disease. Due to the spread of drug resistant parasites there is an urgent need to identify new anti-malaria targets and develop new drugs. We have shown that two enzymes, termed neutral aminopeptidases, are essential to the parasite's survival in the host. In this proposal we will obtain the structure of these enzymes and bring forth novel lead compounds that will form the basis of a new class of anti-malaria treatment.
Rational Design And Development Of New Anthracenedione Derivatives
Funder
National Health and Medical Research Council
Funding Amount
$471,702.00
Summary
Our laboratory has discovered a way to activate the anti-cancer drug mitoxantrone to make it bind to DNA more effectively. This involves pre-activating it with the simple molecule formaldehyde. This concept has enabled us to design new anticancer drugs that are predicted to be more effective at killing cancer cells. In this study we will synthesise these new compounds then test how effectively they bind to DNA, inhibit growth of tumour cells in culture, and inhibit growth of tumours in mice.