Developing Patient Centric Oral Medicines for Neglected Tropical Diseases

Lead Research Organisation: De Montfort University
Department Name: School of Pharmacy

Abstract

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.

Planned Impact

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 .

Publications

10 25 50
 
Description I will report the outcomes after the award has ended.
Exploitation Route The cocrystal approach has been recognised as an effect tool for delivery of medicines with poor water solubility. Several collaborative research projects are under preparing.
Sectors Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description I will complete this section when the project is finished.
First Year Of Impact 2019
Sector Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description Development of patentable nutraceutical cocrysals
Amount £20,000 (GBP)
Organisation De Montfort University 
Sector Academic/University
Country United Kingdom
Start 02/2019 
End 01/2020
 
Description Cocrystal manufacturing (Researchers in Residence) 
Organisation Centre for Process Innovation (CPI)
Country United Kingdom 
Sector Private 
PI Contribution I will work at NFC as RiR (Researchers in Residence) to explore and examine continuous manufacturing methods for cocrystal products.
Collaborator Contribution CPI will provide me access to their facilities relating to formulation and characterisation for the period of my fellowship.
Impact drug design, manufacturing, QbD, engineering
Start Year 2019
 
Description Quadram Institute Bioscience (QIB) 
Organisation Quadram Institute Bioscience
Country United Kingdom 
Sector Academic/University 
PI Contribution We will develop novel cocrystal based nutraceutical products with improved bioavailability
Collaborator Contribution They will test the products in simulated stomach and small intestinal models and human as well.
Impact A collaborative proposal is under preparation.
Start Year 2019
 
Description Tropical diseases: (The London School of Hygiene & Tropical Medicine) 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Faculty of Infectious and Tropical Diseases
Country United Kingdom 
Sector Academic/University 
PI Contribution As formulation scientists, we have developed several cocrystal based formulations with improved bioavailability to treat various diseases, such as malaria and schistomosiasis.
Collaborator Contribution Experts in LSHTM have provided an in-depth understanding of unmet patient needs for the patients infected by tropical diseases, such as malaria and schistomosiasis. Strategic advices have been provided by them to help us understand the desired treatment outcomes as well as the relevant patient therapeutic needs and challenges. Animal experiments have been designed and conducted by LSHTM to test the proof-of-principle of our formulations.
Impact Research paper: M Guo, K Wang, N Qiao, V Yardley, M Li, Investigating Permeation Behavior of Flufenamic Acid Cocrystals Using a Dissolution and Permeation System, Molecular pharmaceutics 15 (9), 4257-4272
Start Year 2019
 
Description University Hospitals of Leicester (UHL) 
Organisation University Hospitals of Leicester NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution We will develop novel cocrystal based anti-viruses medicines to tackle current drugs with low bioavailability.
Collaborator Contribution They will provide the unmet patient needs of current drug treatments and the relevant patient therapeutic needs and challenges.
Impact we have submitted a research grant to British Society for Antimicrobial Chemotherapy, which is currently under review.
Start Year 2019
 
Description Attending Formulation Forum: Disruptive Technologies, 21 - 22 January 2019 at SCI, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Present the research outcomes and foster collaboration
Year(s) Of Engagement Activity 2019
 
Description Research meeting with experts in CPI 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Present the research outcomes to experts in CPI to foster collaboration
Year(s) Of Engagement Activity 2018,2019
 
Description Research meeting with experts in Quadram Institute Bioscience 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Present the research outcomes and discuss potential collaboration.
Year(s) Of Engagement Activity 2019
 
Description Visiting LSHTM 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Attending the research seminars, lectures and workshops to understand the fundamentals of neglected tropical diseases.
Year(s) Of Engagement Activity 2018,2019
 
Description Visiting University Hospitals of Leicester 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Present the research outcomes and foster collaboration.
Year(s) Of Engagement Activity 2018,2019
 
Description Visiting University of Leeds, University of East Anglia, UCL school of pharmacy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact present the research outcomes and foster collaboration
Year(s) Of Engagement Activity 2018,2019