Developing Patient Centric Oral Medicines for Neglected Tropical Diseases

被忽视的热带疾病(NTDS)是由病毒、细菌、原生动物和蠕虫等各种病原体引起的一组多样化的热带感染。治疗非传染性疾病的药物的开发在很大程度上被忽视了，研究和开发投资不足，它们影响着全世界10多亿人，其中大多数是生活在低收入和中等收入国家的农村地区和城市贫民窟的世界上最脆弱的群体。药物治疗，特别是对死亡率最高的三种NTDS(即恰加斯病、人类非洲锥虫病和内脏利什曼病)的药物治疗非常有限、陈旧、有毒和不便，因为需要输液。因此，当务之急是开发高度特异、无毒、低成本的治疗NTDS的口服药物。尽管一些新的候选药物表现出了良好的抗原虫活性，但由于其较差的生物药学性能，特别是在口服剂型方面，很少有化学先导具有进一步开发的潜力。因此，进一步探索这种更有效、更实惠的新一代抗原虫药物是至关重要的，并特别强调开发有效的口服制剂策略。基于PI对药物共晶体的深厚知识/记录，代表了一类用于改善其物理性质(如溶解度和溶出度)的多组分晶体形式，自然会通过这一学科的跳跃来探索开发超生物利用度和低成本口服药物的潜在解决方案的共结晶化方法。活动将包括：(1)参加理学硕士课程中“寄生虫学与昆虫学”和“寄生虫感染免疫学”单元的讲座；(2)参加“寄生虫的实验室诊断”的CPD(持续专业发展)短期课程；(3)学习细胞变异性分析和动物模型体内测试技术；(4)在动物模型中开展青蒿素共晶体的生物利用度研究；(5)与学术人员举行两周一次的会议；(6)出席和参加研究研讨会和会议；(7)访问伦敦热带病医院(HTD)。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，目的是开发长期的多学科研究伙伴关系和解决方案，为非专利疾病的低成本有效的口腔治疗。

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.