Disease Selective Medicines

A major limitation of cancer chemotherapy is their unavoidable toxicity against normal tissues, which result in their dose limitation and a lower than optimal therapeutic activity. Ultimately, this reduces the health benefit for the patient.

In the longer term, cancer therapy is associated with the development of serious adverse effects upon the cardiovascular system. This can lead to cardiac failure and a significant impact upon a patient’s quality of life.

Our current research to address these problems include:

• development of novel cancer medicines which remain inactive until exposed to degradative enzymes located specifically within the cancer, thereby delivering a high efficacious dose of medicine directly to the tumor whilst circumventing detrimental effects to other organs
• identification of the mechanistic basis for cardiac toxicity of cancer medicines
• clinical evaluation of strategies to prevent cardiac toxicity caused by cancer chemotherapy
  

Principal investigator: Dr Jason Gill

Perception of pain and itch is considered as a protective mechanism. However, prolonged pain or itch-related stimulation of the nervous system or other underlying illness (e.g., diabetes) may lead to the development of chronic pathologic condition that is losing its protective character. Current treatment of chronic pain and itch involves the use of a range of different therapeutic strategies, many of which fail to deliver long-term efficacy and tolerability or require dose modification to counteract the adaptive and complex nature of these conditions. 

Despite recent advantages in our understanding of both pain and itch processing, this has yet to translate into improved clinical management of chronic pain and itch sufferers.

Our work focuses on:

• identification of a viable and tractable targets through better understanding of the molecular processes underlying chronic pain and itch
• development of strategies allowing for utilization of other drug classes to improve long-term opioid-mediated relief of chronic pain
• understanding of spinal cord stimulation (SCS) mechanisms and efficacy in neuropathic pain
• understanding of mechanisms underlying dental pain (in collaboration with School of Dental Sciences at Newcastle)
  

Principal investigator: Dr Ilona Obara

Considerable progress in developing new treatments for human immunodeficiency virus (HIV) have been made. But, challenges remain, including viral latency, resistance, and the poor safety profile of many of the current agents. New therapeutic approaches are therefore required.

Our approaches include: 

• development of new therapeutic entities targeting the gp120-CD4 interaction or ribosomal frameshifting, both essential processes in HIV infectivity
• development of allosteric integrase inhibitors against HIV
  

Principal investigators: Dr Mark Ashton and Dr Lauren Molyneux 

Over-reliance and misuse of antibiotics have brought about the prevalence of multi-drug resistant bacteria. This phenomenon has fast become a major global problem. One bacterial disease for which multi-drug resistance is becoming a major issue is Tuberculosis, with the need for improved selective medicines for this disease becoming critical. 

Using a chemical biology approach we are developing novel small molecule inhibitors. These selectively target mycolate bacteria, the causative agent of Tuberculosis.

Principal investigator: Dr Jonathan Sellars

The delivery of many medicines to the skin and their subsequent absorption is limited by physiological and biological factors. This includes the natural skin barrier and microbial biofilms. Several strategies to overcome these problems and circumvent the natural processes have been hypothesized, including:

• prodrugs
• co-drugs
• co-formulations
• microneedles
• nanotechnological devices
• bioresponsive drug release systems
• site-specific drug targeting

The ultimate aim is to improve drug formulation, bioavailability, safety, and patient acceptability.

Our research includes:

• development of drug delivery system or drug formulation strategies to combat biofilm formation and resistance in the skin
• preclinical development of a microneedle biosensor platform for rapid and minimally invasive skin disease detection
• exploration of the medical and pharmaceutical use of lasers as a minimally invasive means of drug delivery
  

Principal investigators: Dr Keng Wooi Ng and Dr Wing Man Lau

Nanoparticle engineering and nanoformulation technologies are rapidly advancing the scope of drug delivery systems. The development of nanotherapies to a personalised level is somewhat revolutionising the field. But a greater appreciation and understanding of these drug delivery strategies are required.

Our studies are focused on the elucidation of these factors and the development of new nanotherapeutic technologies. We also focus on approaches for the treatment of various conditions, including:

• cancer
• cardiovascular diseases
• immune disorders

Our studies also involve diseases of the central nervous system. In particular, we study: 

• opportunities offered through understanding pathophysiolocal processes, to the design and engineering of efficient and safe nanopharmaceuticals
• the role of the innate immune system in relation to nanoparticle performance and safety
• detailed mapping of nanopharmaceutical “structure-activity” relationships at single cell and molecular levels
• long-term concomitant extensive computational network knowledge of genomics and epigenomics of inter-individual variations to nanoformulation performance, and adverse drug and nanomaterial responses
  

Principal investigator: Prof. Moein Moghimi

Metal-Organic-FrameworkS (MOFS) are polymeric, three dimensional structures. They are comprised of metal nodes (e.g. Ag, Au, Fe) with interconnecting organic strands (e.g. bi-arylbenzoic acids). The hydridisation of the organic strands contributes to the framework architecture often leading to accessible internal cavernous space. This has recently drawn significant attention in current research directives. Sequestration of compounds into these cavities, such as CO2 and small molecule drugs has opened up the possibility for new drug delivery systems. The utility of these MOFS is however limited by instability of the cavity and poorer than required biocompatibility.

Our approach to resolve these issues and progress MOFS as a drug delivery platform are:

• synthesis of novel MOFS incorporating high-pressure cross-linking subunits to prevent leaking
• development of new metal nodes and clusters to combat biocompatibility
  

Principal investigator: Dr Jonathan Sellars