Developing Patient Centric Oral Medicines for Neglected Tropical Diseases

被忽视的热带病（NTD）是由病毒、细菌、原生动物和蠕虫等多种病原体引起的一组不同的热带感染。治疗NTD的药物开发在很大程度上被忽视，研发投资不足，影响全球10亿多人，其中大多数是生活在低收入和中等收入国家农村地区和城市贫民窟的世界上最脆弱的人。药物治疗，特别是对死亡率最高的三种NTD（即恰加斯病、非洲锥虫病和内脏利什曼病）的药物治疗非常有限、过时、有毒，并且由于需要输注而不方便。因此，迫切需要开发高度特异性、无毒、低成本和口服的NTD药物。虽然一些新的候选药物已经显示出优异的抗原生动物活性，但由于其较差的生物制药特性，特别是对于口服剂型，很少有化学先导物具有进一步开发的潜力。因此，这是至关重要的，这新一代的更有效的和负担得起的抗原虫剂进一步探索，特别强调开发有效的口服制剂策略。基于PI对药物共晶体的丰富知识/记录，代表一类多组分结晶形式，用于改善其物理性质，如溶解度和溶出速率，通过该学科的跳跃，探索共结晶方法以开发用于NTD的超生物利用度和低成本口服药物的潜在解决方案是很自然的。这些活动将包括：（1）参加硕士课程中“寄生虫学与昆虫学”和“寄生虫感染免疫学”模块的讲座;（2）参加短期持续专业发展（3）学习细胞变异性分析和动物模型体内测试技术;（4）开展青蒿素共晶体动物模型生物利用度研究;（5）每两周与学术人员举行一次会议;（6）出席和参加研究研讨会和会议;（7）访问伦敦的热带病医院。最终，这笔资金将使他作为一名配方/材料科学家，扩大他的专业知识，旨在发展长期的多学科研究伙伴关系和低成本有效的NTD口腔治疗解决方案。

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.