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Feasibility study of a surface-coated lung model to quantify active agent deposition for preclinical studies.
Clinical Biomechanics ( IF 1.4 ) Pub Date : 2020-05-11 , DOI: 10.1016/j.clinbiomech.2020.105029
Philipp Dörner 1 , Philipp M Müller 1 , Jana Reiter 2 , Martin C Gruhlke 2 , Alan J Slusarenko 2 , Wolfgang Schröder 1 , Michael Klaas 1
Affiliation  

BACKGROUND Multiple drug resistance of a growing number of bacterial pathogens represents an increasing challenge in conventional curative treatments of infectious diseases. However, the development and testing of new antibiotics is associated with a high number of animal experiments. METHODS A symmetrical parametrized lung test rig allowing the exposure of air-passage surfaces to antibiotics was designed and tested to demonstrate proof-of-principle with aerosols containing allicin, which is an antimicrobial natural product from garlic. An artificial lung surface is coated with bacteria embedded in a hydrogel and growth inhibition is visualized by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, that is reduced from colourless to the dark blue formazan in the presence of metabolically active, living cells. A nebulizer is used to generate the aerosols. FINDINGS The results show that allicin has an antibiotic effect as an aerosol and that the deposition pattern of the active agent occurred mainly around the carinal regions. INTERPRETATION The model represents an integral system for continuous, spatial detection of aerosol deposition and allows the analysis of bacterial behaviour and the toxicity of the active agent. Thus, the deposition of antimicrobial aerosols on the bronchial surfaces is characterized in preliminary tests without any animal experiments.

中文翻译:

为临床前研究量化表面涂层肺模型以量化活性剂沉积的可行性研究。

背景技术在传染病的常规治疗中,越来越多的细菌病原体的多重耐药性代表了越来越大的挑战。但是,新抗生素的开发和测试与大量的动物实验有关。方法设计并测试了对称的参数化肺部测试设备,该设备可以使空气流通的表面暴露于抗生素中,并进行了测试,以证明含有大蒜素的气雾剂的原理证明,大蒜素是大蒜的天然抗菌产品。人工肺表面涂有嵌入水凝胶中的细菌,并通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物可视化生长抑制作用,该溴化物从无色变成深蓝色的甲maz。代谢活跃的活细胞的存在。使用雾化器产生气雾剂。结果结果表明,大蒜素作为气雾剂具有抗生素作用,并且活性剂的沉积模式主要发生在隆起区域附近。解释该模型代表了一个用于连续,空间检测气溶胶沉积的整体系统,可以分析细菌的行为和活性剂的毒性。因此,在没有任何动物实验的初步测试中表征了抗菌气雾剂在支气管表面的沉积。气溶胶沉积的空间检测,并可以分析细菌行为和活性剂的毒性。因此,在没有任何动物实验的初步测试中表征了抗菌气雾剂在支气管表面的沉积。气溶胶沉积的空间检测,并可以分析细菌行为和活性剂的毒性。因此,在没有任何动物实验的初步测试中表征了抗菌气雾剂在支气管表面的沉积。
更新日期:2020-05-11
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