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

利什曼病是由利什曼原虫属的原生动物寄生虫引起的一种重要的“被忽视的热带疾病”。有五种临床形式，范围从局部皮肤利什曼病（CL）到致命的内脏利什曼病（VL）。全世界有3.5亿多人被认为处于危险之中，目前有1 200万人受到感染，经济损失估计为200万第纳尔，在寄生虫病中，只有疟疾和淋巴丝虫病超过健康挑战。因此，利什曼病已被世界卫生组织分类为I类：新兴或不受控制的疾病。特别是，由于其作为艾滋病患者的重要合并感染的地位以及艾滋病毒和利什曼原虫属物种的流行重叠，感染的传播和严重程度加剧。在印度，尽管政府做出了相当大的努力，但VL仍然是90个地区的主要健康危害，而CL不是一种应报告的疾病，是一种被忽视的“被忽视的疾病”。利什曼原虫感染的治疗是困难的，所有形式都需要漫长、痛苦和昂贵的药物治疗过程。这些疾病状态所带来的挑战由于可用的少数有效药物经常表现出严重的、可能致命的副作用而加剧。因此，需要有更好的输送方式的新药。在这个英国-印度合作项目中，汇集了化学，制药学，配方科学，寄生虫学和医学人类学，我们将通过开发具有更好管理模式的新型活性抗利什曼原虫化合物来应对这些挑战。我们将使用最先进的结晶和配方技术，为每种化合物提供新的口服和局部给药方法。这一关键方面将由流行社区内的社区参与和当地卫生保健专业人员指导，以确定如何使受影响人群接受药物。重要的是，为了帮助克服耐药性的可能性，将设计能够同时给予两种不同药物的联合治疗的输送装置。

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.