Patient-centric supramolecular formulations of new anti-leishmanial drugs for Indian Communities

Lead Research Organisation: Durham University
Department Name: Chemistry

Abstract

Leishmaniasis is an important 'Neglected Tropical Disease' caused by protozoan parasites of the genus Leishmania. There are five clinical forms which range from localized cutaneous leishmaniasis (CL) to fatal visceral leishmaniasis (VL). With over 350 million people world wide considered at risk, 12 million people currently infected and an economic cost that can be estimated in terms of 2 million DALYs the health challenge is only surpassed amongst parasitic diseases by malaria and lymphatic filariasis. Consequently, the leishmaniases have been classified by the World Health Organisation as Category I: emerging or uncontrolled diseases. In particular, the spread and severity of infection is exacerbated by its status as an important co-infection of AIDS patients and the overlap in prevalence of HIV and Leishmania species.

In India, despite considerable government effort VL is still a major health hazard in 90 regions whilst CL, not being a notifiable disease, is a neglected 'neglected disease'. The treatment of leishmanial infections is difficult with all forms requiring a long, painful and costly course of drug therapy. The challenge presented by these disease states is heightened by the fact that the few efficacious drugs available often exhibit serious, potentially fatal, side-effects. New medicines with better modes of delivery are therefore required.

In this UK-India collaborative project, that brings together chemistry, pharmaceutics, formulation science, parasitology and medical anthropology, we will address these challenges by developing novel active antileishmanial compounds with better modes of administration. We will use state-of-the-art crystallisation and formulation technologies to enable new oral and topical delivery methods for each compound. This key aspect will be directed by community engagement within endemic communities and local health care professionals to define what makes a drug acceptable to the affected populations. Significantly, to help overcome the potential for resistance to arise, the design of delivery devices that enable combination therapies in which two different drugs are dosed simultaneously will be undertaken.

Planned Impact

The leishmanises are responsible for high mortality and morbidity among the world's poorest populations and is a particular health challenge in India. Whilst the treatment of visceral leishmanisis (kalazar) in India has greatly improved in recent times the other forms of the disease, notably PKDL and CL, remain neglected neglected diseases and represent a serious reservoir of infection. For all forms of leishmanais, there is no vaccine available and we still rely on old toxic drugs requiring impractical expensive modes of administration poorly designed for the communities within which they have to work. This project aims to address these challenges. Reflecting this the beneficiaries of this research include:

Healthcare professionals and their patients (particularly the poorest Indian public): who will ultimately benefit from the availability of new treatments for leishmania that can be administered in a community setting. In a knock on effect, health services and related organisations and the general economy will gain from reduced rates of (re)infection, lower costs for treatments and fewer days lost to ill-health.

The pharmaceutical industry, notably our collaborators in both India and the UK who will benefit from new product portfolios providing jobs and income to sustain this vital component of both countries economies. Recognising that this is a global problem and the close similarities with the other kinetoplastid infections this research has the potential to open new markets for early adopters. In addition the generic techniques and new predictive models developed in drug delivery and community health care will provide new insights that can be applied to other disease states.

Through publication and conference presentations by members of the consortium the community will be informed of these advances made. Through this process other scientists working related diseases will benefit from the increased understanding and the tools and technologies developed that can be applied to other systems.

The PDRAs working on this project will gain exposure to multi- and interdisciplinary science in a bilateral fashion including collaboration with industry. Such international and intersectoral experience will benefit them in future careers.

Finally, the academics working on this project will gain from the new contact made and the exposure to other branches of social, clinical and physical science which will be of great benefit in the development of new research lines.

Publications

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