Evaluating the Local Response of a Novel Injectable Capsule for Drug Delivery in the Trachea.

OBJECTIVE: Innovative therapies are needed to improve the treatment of laryngotracheal stenosis. This study investigated the local tissue response of a novel injectable drug delivery platform in a leporine tracheal model. METHODS: Dye-loaded polymer (empty) implants were delivered into the pretracheal tissue of three New Zealand White rabbits using an 18-gauge needle and custom applicator to simulate peritracheal delivery adjacent to tracheal stenosis. Three additional rabbits underwent tracheal injury via electrocauterization to serve as comparative injury controls, and three additional rabbits were included as no-implant, no-injury tracheal controls. Animals underwent laryngoscopy and bronchoscopy on Days 0 and 14 to evaluate the primary outcome of local airway safety after implant placement. Secondary outcomes included ultrasound implant localization, indentation mapping of tracheal wall structural stiffness, and histological assessment. RESULTS: Implant-treated tracheas (n = 3) maintained lumen patency and organized tissue architecture without visible stenosis or microscopic inflammation, whereas injured tracheas (n = 3) demonstrated luminal distortion and disorganized early remodeling. Implant location was confirmed by ultrasound. Indentation mapping showed lower mean anterior and posterior tracheal wall stiffness in implant-treated specimens (5.28 and 4.47 mN/mm, respectively) compared with injured specimens (37.38 and 11.20 mN/mm, respectively). Posterior mucosal thickness was also lower in implant-treated tracheas than injured tracheas (31.02 vs. 56.07 μm). Overall, the implants did not appreciably alter the native tracheal structure. CONCLUSION: This novel injectable platform was well tolerated in the pretracheal space and preserved native tracheal structure, supporting future studies of therapeutic-loaded implants for stenosis mitigation and treatment. LEVEL OF EVIDENCE: NA.