Developing Patient Centric Oral Medicines for Neglected Tropical Diseases

Neglected tropical diseases (NTDs) are a diverse group of tropical infections caused by a variety of pathogens such as viruses, bacteria, protozoa and helminths. Development of drugs to treat NTDs have been largely overlooked and received insufficient research and development investment, they affect more than one billion people worldwide, the majority are the world's most vulnerable living in rural areas and urban slums in low-income and middle-income countries. The drug treatments, in particular for the three NTDs with highest rates of death (i.e. Chagas's disease, human African trypanosomiasis and visceral leishmaniasis), are very limited, dated, toxic and inconvenient because of requirement of infusion delivery. It is therefore imperative that highly specific, non-toxic, low cost and oral drugs are developed for NTDs. Although some new drug candidates have shown excellent antiprotozoal activities, few chemical leads have the potential for further development due to their poor biopharmaceutical properties, in particular for oral dosage forms. Therefore, it is of critical importance that this new generation of more effective and affordable antiprotozoal agents are explored further, with particular emphasis on developing effective oral formulation strategies. Based on the PI's strong knowledge/record of pharmaceutical cocrystals, representing a class of multi-component crystalline forms for improvement of their physical properties such as solubility and dissolution rates, it is natural to explore cocrystallisation approach for potential solutions of development of super-bioavailability and low cost oral medicines for NTDs through this discipline hop. The activities will include: (1) Attending lectures in the modules of "parasitology & entomology" and "immunology of parasitic infection" in MSc courses; (2) Attending a short CPD (Continuing Professional Development) course of "Laboratory diagnosis of Parasites"; (3) Learning cell variability assays and in-vivo testing techniques in animal models; (4) Carrying out bioavailability study of Artemisinin cocrystals in animal models; (5) Biweekly meeting with academic staff; (6) Attending and participating in research seminars and conferences; (7) Visiting the Hospital for Tropical Diseases (HTD) in London. Ultimately, this funding would allow him, as a formulation/material scientist, to widen his expertise with the aim of developing long term multidisciplinary research partnerships and solutions for low cost effective oral treatments for NTDs.

The knowledge, skills and findings obtained by the PI from the discipline hop will have a direct impact on development of novel medicines for treatments of NTDs and subsequently have significant impact on economy, people and society.

More than one billion people worldwide are affected by NTDs, encompassing some of the world's most vulnerable populations living in rural areas and urban slums of low-income and middle-income countries. NTDs can cause significant morbidity and mortality, leading to severe disfigurement and disabilities. NTDs are also recognized as a contributor to poverty since they can impair intellectual development in children, reduce school enrolment and hinder economic productivity by limiting the ability of infected individuals to work. The drug treatments, in particular for the three NTDs with highest rates of death (i.e. Chagas's disease, human African trypanosomiasis and visceral leishmaniasis), are very limited, dated, toxic and inconvenient because of requirement of infusion delivery. It is therefore imperative that a highly specific, non-toxic, low cost and oral drug is developed for NTDs. However, large pharmaceutical companies have abandoned this line of research, from pipeline to clinical trials to market, due to the absence of commercial markets. Only 1.3% of new drugs developed by the global pharmaceutical sector over three decades were directly aimed at these diseases. Therefore, third sector organisations, like us the universities, are particularly well placed to target and tackle NTDs. This project would thus provide the PI with an opportunity to provide solutions for NTD treatments that strengthen the UK business sector, retain jobs, and deliver improved products. Ultimately the project will lead to development of superior quality and lower cost oral NTD medicines, which will have tremendous impacts on human health and wellbeing. Too often in poor countries people have been forced to watch patients die because they cannot afford the drugs that could improve, extend, or save their lives. Access to NTD treatments can avoid catastrophic health expenditure representing a route out of poverty for households. It can also reduce financial burden on health systems in almost all countries, including UK's NHS.

The project deliverables are closely aligned with the EPSRC's Healthcare Technologies Theme addressing the grand challenge of Developing Future Therapies through development, characterisation and processing of advanced materials with novel chemical, physical or mechanical properties to enhance the efficacy and precision of therapies and reduce the risk to patients from side effects. The proposal draws on the long-standing and emerging research at De Montfort University in drug design and discovery, formulation science and Quality by Design (QbD) for drug product and process development to explore novel solutions for NTDs. Outputs from the hop activities will enable the PI who is in EPSRC disciplines of material and formulation sciences to better identify the unmet patient needs and treatment challenges of NTDs, understand the drivers for the treatment challenges where cocrystallisation would be deployed and foster multidisciplinary research, all of which are encouraged in the Maxwell Review .