Controlled Drug Delivery to Tracheal Tissue and the Laryngotracheal Complex from a Novel Coated Endotracheal Tube Augmenting SARS-CoV-2 Care

Advanced airway devices to deliver therapeutics directly from endotracheal tubes are lacking in the treatment of patients with acute respiratory distress syndrome (ARDS, from SARS-CoV-2 [COVID-19] or other etiologies), extended periods of intubation, prolonged field care, and multi-domain operations. Prolonged endotracheal intubation poses numerous challenges to clinicians to include long-term breathing, voice, and swallow complications, acute laryngeal injury (ALgI) including tracheal or posterior glottic stenosis, and ventilator associated pneumonia. No current mitigating technologies allow for airway maintenance with reduced mucosal injury and local drug delivery for management and prevention of lung function. This project aims to employ a polymer-mesh coated endotracheal tube platform capable of delivering various antifibrotic, antiviral, anti-inflammatory, and other therapeutics. We hypothesize that continuous delivery of therapeutics will lead to improve local wound healing, resulting in more native biomechanical tissue properties and decreased fibrosis and stenosis. A total of 81 swine underwent transglottic stent placement divided into groups of injured/non-injured and traditional endotracheal tubes or ones with electrospun fibers loaded with dexamethasone, Roxadustat, acyclovir, anti-SMAD3 SiRNA, or empty and left in place for varying durations. Less fibrosis and inflammation was present on histologic evaluation of injured larynges when therapeutic-loaded polymer tubes were employed compared to traditional endotracheal tubes, particularly in the case of dexamethasone. Biomechanical testing also revealed more native tissue properties when employing dexamethasone-loaded polymer endotracheal tubes. Collectively, these data suggest a promising role for employing electrospun, polymer coated endotracheal tubes loaded with dexamethasone or other therapeutics.