Light-triggered precision drug dosing from PVC endotracheal tube biomaterials

目前，重症监护病房（ICU）中的患者因肺炎死亡率很高。ICU医护人员面临的一个主要挑战是让病人免受感染。病人经常服用药物来削弱他们的免疫系统，例如，允许身体接受移植而不是排斥它。不幸的是，这意味着他们的身体特别容易受到感染。另一个复杂的问题是，病人通常有几个医疗设备将他们的身体连接到专门的设备。其中之一是气管内（ET）管，它插入患者的气管，将空气从人工呼吸机引导到肺部。ET管主要由PVC制成，细菌能够相对容易地附着在管的表面，在那里它们迅速生长并发育成称为生物膜的大菌落。这类似于在牙齿上形成的菌斑。由于生物膜对抗生素的抗性及其在ET管内壁上的位置，生物膜极难被杀死。当通风空气被泵入患者的ET管时，一些生长在生物膜中的细菌从表面脱落并被带入肺部，从而发生肺炎。我们从ICU中死亡或康复的患者身上获得了ET管，并调查了有多少和什么类型的细菌附着在管上。这些研究使我们能够发展我们的研究计划，通过改变ET管的表面来防止细菌感染ET管，从而减少ICU中死亡的患者数量。我们仍然会使用针对这些细菌的特异性和选择性抗生素，但不是通过注射或片剂给药，而是将它们化学结合到ET管的表面。一些研究人员已经将抗生素添加到ET管聚合物中，但这并不能在表面提供足够的抗菌活性，并且由于添加的物质，管本身可能会变得机械较弱。这种弱化可能导致ET管的塌陷和患者气道的阻塞。在我们的新方法中，我们将首先将抗生素结合到细菌将要附着的表面。然后，当我们需要的时候，我们可以通过从光纤中照射光线来打破抗生素与塑料表面的结合。在实践中，医生将通过患者的ET管中的开口插入光纤，光将被引导到细菌附着的内壁。其中一些“光依赖”键会断裂，在附着的细菌处释放出非常高浓度的抗生素。我们之前已经进行了这种类型的研究工作，将抗生素附着到聚合物上，并且还与光激活表面和分子一起工作。有鉴于此，我们有信心能够通过降低肺炎发展的机会来帮助ICU患者恢复良好，并通过开发新型ET管用于制造和商业化来帮助该国的医疗器械行业。

There is currently a high death rate due to pneumonia of patients in Intensive Care Units (ICU). A major challenge facing the medical staff in ICU is to keep the patient free from infection. The patient is often taking medicines to weaken their immune systems to allow, for example, a transplant to be accepted by the body instead of rejecting it. Unfortunately this means that their bodies are particularly susceptible to infection. A further complication is that the patient often has several medical devices connecting their body to specialised equipment. One of these is an endotracheal (ET) tube, which is inserted into the patient's trachea channelling air from an artificial ventilator into the lungs. ET tubes are mostly manufactured from PVC, and bacteria are able to attach relatively easily to the surface of the tube, where they rapidly grow and develop into large colonies known as biofilms. This is similar to the bacterial plaque which forms on the teeth. The biofilm is extremely difficult to kill due its resistance to antibiotics and its location on the inside wall of the ET tube. When ventilated air is pumped into the patient's ET tube some of the bacteria growing in the biofilm are shed from the surface and carried down into the lungs and pneumonia develops. We have obtained ET tubes from patients who have either died or recovered in ICU and investigated how much and what types of bacteria are attached to the tubes. These studies have allowed us to develop our research plan to prevent bacteria infecting the ET tube by modifying its surface and so reduce the number of patients dying in ICU.We will still use specific and selective antibiotics against these bacteria, but instead of giving them by injection or as tablets we will chemically bind them to the surface of the ET tube. Some researchers have added antibiotics into the ET tube polymer, but this does not provide sufficient antimicrobial activity at the surface and the tube itself can become mechanically weaker because of the added substances. This weakening can cause collapse of the ET tube and blockage of the patient's airway. In our new approach, we will firstly bind the antibiotics to the surface where the bacteria are going to attach. Then, when we need to, we can break the bonds binding the antibiotic to the plastic surface by shining light from a fibre optic on them. In practice, the doctor will insert a fibre optic through an opening in the patient's ET tube and light will be directed to the inner walls where the bacteria attach. Some of these 'light-dependent' bonds will break releasing antibiotic in a very high concentration right at the attaching bacteria. We have carried out this type of research work before with attaching antibiotics to polymers and have also worked with both light-activated surfaces and molecules. Given this, we have confidence that we will be able to help patients in ICU to recover well by reducing the chance of pneumonia developing and also help the medical device industry in this country by developing a new type of ET tube for manufacture and commercialisation.