Inhalable nanomedicines for treatment of tuberculosis

用于治疗结核病的可吸入纳米药物

• 批准号: 2275016
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2275016
• 关键词: Inhalable; nanomedicines; treatment; tuberculosis

Abstract: Date: 16/03/2022The rapid spread of multi drug-resistant tuberculosis (TB) is a major threat to global public health. According to WHO ~1.8 million people die every year of TB, with an estimated 9.8 million new infections per year, which is exacerbated due to the number of patients infected with HIV/AIDs. Treatment of TB is lengthy (6-months for the short course), with the development of drug resistant organisms (Mycobacterium tuberculosis (M.tb)) due to incomplete or inappropriate treatment. The aim of the PhD is to develop an aerosolised, inhalable nanomedicine that delivers first line anti-tuberculous drugs embedded within antibacterial silver (Ag) nanoparticles (NPs) locally to the M.tb inside the host, infected macrophages in the peripheral respiratory zone. The antibacterial Ag NPs can permeabilise the M.tb cell envelope barrier to increase drug efficacy - with clinical potential to reduce the drug doses needed for treatment, avoid systemic side effects and increase patient compliance and reduce development of multidrug resistance. The engineered drug system will consist of a poly(lactic-co-glycolic acid) (PLGA) microparticle-encapsulation platform into AgNPs and first-line antibiotics (alone and in combination) will be loaded. The early focus will be given to first-line antibiotics, however the platform will be tailored for later inclusion of emerging drugs that treat drug resistant TB. The student will test the nanodrug in unique in vitro human co-culture of models of the human alveolar unit infected with M.tb, to assess its efficacy and safety and how it interacts with the host's immune system to facilitate successful microbial killing. The student will develop aerosol exposure systems to deliver the microparticle-drug formulations in vitro; medical drug delivery devices - either nebulisers or dry-powder inhalers - will be tested as potential delivery systems for use in the clinic to achieve therapeutically inhaled drug doses.Relevant EPSRC research areas: Analytical science, Particle technology, Sensors and instrumentation, Clinical technologies (excluding imaging)

摘要：Date：16/03/2022耐多药结核病（TB）的迅速蔓延是对全球公共卫生的主要威胁。据世卫组织统计，每年约有180万人死于结核病，估计每年有980万新感染病例，由于感染艾滋病毒/艾滋病的患者数量增加，这一情况更加严重。结核病的治疗是漫长的（短期为6个月），由于不完全或不适当的治疗，会产生耐药性微生物（结核分枝杆菌（M.tb））。博士的目的是开发一种雾化的，可吸入的纳米药物，将嵌入抗菌银（Ag）纳米颗粒（NP）的一线抗结核药物局部递送到宿主内的结核分枝杆菌，感染外周呼吸道区的巨噬细胞。抗菌Ag NP可以透化结核分枝杆菌细胞包膜屏障以增加药物功效-具有减少治疗所需的药物剂量、避免全身副作用和增加患者依从性并减少多药耐药性的发展的临床潜力。工程药物系统将由聚（乳酸-羟基乙酸）（PLGA）微粒封装平台组成，将其封装到AgNP中，并将加载一线抗生素（单独和组合）。早期的重点将放在一线抗生素上，但该平台将针对治疗耐药结核病的新兴药物进行量身定制。学生将在感染结核分枝杆菌的人类肺泡单位模型的独特体外人类共培养物中测试纳米药物，以评估其有效性和安全性，以及它如何与宿主的免疫系统相互作用，以促进成功的微生物杀灭。学生将开发气溶胶暴露系统，以在体外提供微粒药物制剂;医疗药物输送设备-无论是雾化器或干粉吸入器-将被测试为潜在的输送系统，用于临床，以实现治疗吸入药物剂量。相关EPSRC研究领域：分析科学，粒子技术，传感器和仪器，临床技术（不包括成像）

项目成果

Approaches to treating tuberculosis by encapsulating metal ions and anti-mycobacterial drugs utilizing nano- and microparticle technologies.

• DOI: 10.1042/etls20190154
• 发表时间: 2020-12-17
• 期刊: Emerging topics in life sciences
• 影响因子: 3.8
• 作者: Alzahabi KH;Usmani O;Georgiou TK;Ryan MP;Robertson BD;Tetley TD;Porter AE
• 通讯作者: Porter AE