Electrospun composite-coated endotracheal tubes with controlled siRNA and drug delivery to lubricate and minimize upper airway injury

• Published in: Biomaterials Vol. 309; p. 122602
• Main Authors: Miar, Solaleh, Gonzales, Gabriela, Dion, Gregory, Ong, Joo L., Malka, Ronit, Bizios, Rena, Branski, Ryan C., Guda, Teja
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2024
• Subjects: Animals; Coated Materials, Biocompatible - chemistry; Dexamethasone - pharmacology; Drug Delivery Systems; Endotracheal tube; Humans; Intubation, Intratracheal; Local drug delivery; Polyesters - chemistry; RNA, Small Interfering; siRNA delivery; SMAD3; Swine; Upper airway; siRNA delivery; Local drug delivery; SMAD3; Endotracheal tube; Upper airway
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2024.122602

Endotracheal Tubes (ETTs) maintain and secure a patent airway; however, prolonged intubation often results in unintended injury to the mucosal epithelium and inflammatory sequelae which complicate recovery. ETT design and materials used have yet to adapt to address intubation associated complications. In this study, a composite coating of electrospun polycaprolactone (PCL) fibers embedded in a four-arm polyethylene glycol acrylate matrix (4APEGA) is developed to transform the ETT from a mechanical device to a dual-purpose device capable of delivering multiple therapeutics while preserving coating integrity. Further, the composite coating system (PCL-4APEGA) is capable of sustained delivery of dexamethasone from the PCL phase and small interfering RNA (siRNA) containing polyplexes from the 4APEGA phase. The siRNA is released rapidly and targets smad3 for immediate reduction in pro-fibrotic transforming growth factor-beta 1 (TGFϐ1) signaling in the upper airway mucosa as well as suppressing long-term sequelae in inflammation from prolonged intubation. A bioreactor was used to study mucosal adhesion to the composite PCL-4APEGA coated ETTs and investigate continued mucus secretory function in ex vivo epithelial samples. The addition of the 4APEGA coating and siRNA delivery to the dexamethasone delivery was then evaluated in a swine model of intubation injury and observed to restore mechanical function of the vocal folds and maintain epithelial thickness when observed over 14 days of intubation. This study demonstrated that increase in surface lubrication paired with surface stiffness reduction significantly decreased fibrotic behavior while reducing epithelial adhesion and abrasion. [Display omitted] •Inflammation and fibrosis in upper airway prevented by multimodal local delivery.•Hydrogel coatings retained by electrospun layer support lubrication against mucosa.•Drug delivery of siRNA polyplexes from hydrogel demonstrated silencing efficacy.•Low surface stiffness prevents oral mucosal abrasion and epithelial adhesion.•Electrospun fibers allow solid diffusion and controlled corticosteroid delivery.