Polymersomes to enhance therapeutic options for treating intracellular bacterial infections

军事人员由于在部署环境中接触地方病、由于战场受伤或由于接触故意释放生物战剂而接触传染物的风险可能很高。许多细菌性死亡病原体的一个共同特点是它们是细胞内病原体，感染剂量低，死亡率高。例如，引起类鼻疽病的假伯克氏菌，引起土拉菌病的土拉弗朗西斯菌，引起鼠疫的鼠疫耶尔森菌和引起Q热的伯纳克氏菌。由这些疾病引起的感染本身就难以治疗，目前的治疗选择有限，而且往往效率低下。[1,2,3]此外，日益增长的抗生素滥用和过度使用导致了多重耐药细菌的加速出现和现有治疗方法的失败因此，迫切需要发展在军事环境中易于部署和管理的新的有效治疗方法。该项目的目的是研究一种新的基于pm的包封技术，以提高治疗BW感染的现有疗法的生物利用度。由于减轻抗生素输送的后勤负担在军事行动背景下至关重要，因此研究重点将是调查和开发可自行给药的配方，例如口服或吸入途径。该兼职博士的项目活动将主要在Dstl进行。该项目将利用南安普顿大学现有的PM配方专业知识和Dstl的设施，这将允许使用3级（CL3） BW病原体进行体外和体内工作。

The risk of exposure to an infectious agent for military personnel can be high as a consequence of exposure to endemic diseases in deployment environments, as a consequence of battlefield injuries or due to exposure to a deliberate release of a biological warfare (BW) agent. A common feature of many bacterial BW agents is that they are intracellular pathogens with low infectious dose and high mortality rates. Examples include Burkholderia pseudomallei, the causative agent of melioidosis, Francisella tularensis, the causative agent of tularaemia, Yersinia pestis, the causative agent of plague and Coxiella burnetii, the causative agent of Q fever. Infections caused by these are inherently difficult to treat and current therapeutic options are limited and often inefficient.[1, 2, 3] Furthermore, the ever growing misuse and overuse of antibiotics had led to the accelerating emergence of multi-drug resistant bacteria and failure of existing therapeutics.[4] Consequently, there is an immediate medical need for the development of new effective treatments [5] which can be easily deployed and administered in a military setting. The aim of this project will be to investigate novel PM-based encapsulation technology to enhance bioavailability of existing therapeutics for the treatment of BW infections. Since reducing the logistical burden of antibiotic delivery is essential in a military operational context, a research focus will be the investigation and development of formulations that can be self-administered, for example by oral or inhalational routes. The project activities of this part-time PhD will be largely conducted at Dstl. The project will capitalise on access to existing PM formulation expertise at the University of Southampton and the facilities at Dstl which will allow in vitro and in vivo work to be conducted using containment level 3 (CL3) BW pathogens.