(338f) Injectable, Tunable Therapeutic Implant for Laryngeal Disease Treatment

Laryngeal diseases, including vocal fold scarring and airway stenosis, require frequent local injections of corticosteroids. However, the effectiveness of current corticosteroid delivery methods is limited by factors such as short duration of action, discomfort, and costs associated with repeated procedures.

To address these limitations, we have developed two types of implants: (i) sustained-release capsule implants and (ii) light-activated capsule implants for local delivery of dexamethasone (Dex). For the sustained-release capsule implants, four different biodegradable polymers (polycaprolactone, poly(lactic acid), 90:10 poly(lactic-co-glycolide), and 50:50 poly(lactic-co-glycolide)) were used as capsule materials. The release profiles of Dex from these capsules were compared, and the 50:50 poly(lactic-co-glycolide) showed the fastest release. The permeability and partition coefficient of each polymer were measured, and it was found that the release of Dex through the capsule membrane was primarily due to “solution-diffusion” rather than diffusion through pores. The hydrophobicity of the polymer sheet was found to correlate with the drug release kinetics, with more hydrophobic polymers exhibiting slower release rates for the hydrophilic drug Dex. In vitro cell studies demonstrated the effective suppression of pro-inflammatory cytokine IL-6 levels using the Dex-loaded implant, indicating its potential therapeutic benefits with minimal toxicity.

Light-activated capsule implants were developed using light-activated liposomes encased within biodegradable polycaprolactone capsules. These liposomes, responsive to laser irradiation, facilitated controlled drug release, modulated by the duration of irradiation. Our experiments demonstrated successful drug release from these implants using a near-infrared (NIR) pulsed laser at 100 mW, connected via an optical fiber. When tested in a tissue phantom resembling laryngeal tissue in light transparency, the release kinetics exhibited a 4% reduction with every 2 mm increase in tissue depth. Additionally, in vivo studies on rabbit vocal folds revealed that the implants remained in place throughout the 14-day study period, with histology results indicating no adverse effects on the local tissue.

Overall, the development of the biodegradable polymer capsule for long-term release of Dex holds promise for improving the treatment of voice disorders, airway stenosis, and other related conditions.