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

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.