Overseas Travel Grant - Research visit to Louvain Drug Research Institute at the Universite catholique de Louvain

慢性伤口对个人、卫生保健系统和整个社会造成了重大且往往被低估的负担。据估计，NHS在治疗慢性伤口上花费了50亿英镑，在英国大约有220万人患有慢性伤口。这些慢性伤口极易感染。无法愈合的伤口患者经常接受抗生素治疗，以治疗复发性感染伤口。导致这些感染的细菌，如耐甲氧西林金黄色葡萄球菌（MRSA）和铜绿假单胞菌，通过隐藏在细胞内，导致持续和反复感染，从而逃避免疫系统和抗生素治疗，将这些细胞转化为感染库。由于细胞内环境对抗生素的不同敏感性以及在细胞环境中达到有效浓度的挑战，通过持续存在于细胞内环境而逃避免疫系统的细菌很难用传统的抗生素治疗方法治疗。需要新的治疗策略来提高抗生素治疗细胞内感染的有效性，目前需要长时间和反复的抗生素治疗。这些重复治疗通过无效地清除被感染个体的病原体和修改其微生物组，增加其体内耐药细菌的数量，从而有助于抗菌素耐药性。冷等离子体技术是一种创新的消毒感染表面和慢性感染伤口的新方法。冷等离子体指的是将电能输入到氦气等气体中产生的部分电离气体，产生的等离子体适合治疗像我们的皮肤这样的热敏表面。目前已有一系列可用于治疗感染伤口的设备。目前，这项技术的抗菌活性得到了很好的表征，但没有发表的数据表明它对细胞内感染细胞的影响与抗生素治疗同时进行。该项目的目的是研究冷等离子体治疗感染细胞的效果，随后冷等离子体沉积一种浸渍有抗生素纳米颗粒的水凝胶敷料，以提高抗生素治疗细胞内感染和慢性伤口的效力和有效性。这将减少为有效清除持续性组织感染以及局部治疗感染所需的抗生素治疗。为了实现这一目标，必须建立一个合适的细胞内感染模型。在鲁汶天主教大学（Universite’Catholique de Louvain）的鲁汶药物研究所，他们开发了用于细胞内感染的抗生素药效学模型。这次对该机构的研究访问将使我了解和掌握该模型的使用，从而实现我的研究计划的目标，并与一家世界领先的机构在抗生素及其感染细胞的药效学方面开展国际合作。

Chronic wounds impose a significant and often underestimated burden to the individual, the healthcare system and society as a whole. It has been estimated that the NHS spends £5 billion on treating chronic wounds with approximately 2.2 million people living with chronic wounds in the UK. These chronic wounds are extremely susceptible to infection. With sufferers of non-healing wounds regularly receiving antibiotic treatment for recurring infected wounds. Bacteria responsible for these infections such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa have the capacity to evade the immune system and antibiotic treatment by hiding within cells resulting in persistent and recurrent infections transforming these cells into reservoirs of infection. Bacteria that evade the immune system by persisting in the intracellular environment are difficult to treat with traditional antibiotic therapies due to the varied susceptibility to antibiotics within the intracellular environment as well as the challenge of achieving effective concentrations of antibiotics within the cellular environment. New treatment strategies are required to increase the effectiveness of antibiotics for intracellular infection treatments, that currently require lengthy and repeated antibiotic treatments. These repeated treatments contribute to antimicrobial resistance through ineffective clearance of the pathogen from the infected individual and modification of their microbiome increasing the population of resistant bacteria within their body. Cold plasma technology is an innovative and new approach for the disinfection of infected surfaces and chronic infected wounds. Cold plasma refers to a partially ionised gas generated from the input of electrical energy into a gas such as helium, creating a plasma suitable for treating heat sensitive surfaces like our skin. There is already a range of devices available for treatment of infected wounds. Currently the antibacterial activity of this technology is well characterised however there is no published data on its effects on intracellular infected cells alongside antibiotic treatments. The aim of this project is to investigate the efficacy of cold plasma treatment of infected cells with subsequent cold plasma deposition of a hydrogel dressing impregnated with antibiotic nanoparticles, to improve the potency and effectiveness of antibiotics for treatment of intracellular infections and chronic wounds. This will result in a reduction of the required antibiotic treatments for the effective clearance of persistent tissue infections as well as localised treatment of the infection. In order to achieve this aim a suitable intracellular infection model must be developed. At the Louvain Drug Research Institute, Universite' Catholique de Louvain, they have developed antibiotic pharmacodynamic models for intracellular infections. This proposed research visit to this Institution will result in an understanding and expertise in the use of this model in order to fulfill the aims of my research program as well as developing international collaboration with a world-leading Institution in antibiotics and their pharmacodynamics in infected cells.