Long term behavior of dexamethasone-loaded cochlear implants: In vitro & in vivo

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Otolaryngology

Background:

• Silicone-based cochlear implants offer potential for local, controlled dexamethasone delivery to treat hearing loss.
• Achieving very long drug release periods (years/decades) for these implants presents significant product optimization challenges.
• Limited knowledge exists regarding the long-term behavior of these systems, including drug release kinetics and dimensional stability.

Purpose of the Study:

• To evaluate the long-term in vitro and in vivo behavior of silicone-based cochlear implants loaded with dexamethasone.
• To understand drug release patterns, swelling/shrinking properties, and the underlying mechanisms.
• To assess the feasibility of predicting long-term drug release for product optimization.

Main Methods:

• Cylindrical cochlear implants with varying dimensions and dexamethasone loading (0-10%) were fabricated via injection molding.
• In vitro drug release was monitored in artificial perilymph at 37°C for over 3 years.
• Implants were characterized using optical microscopy, X-ray diffraction, and Raman imaging before and after in vitro/in vivo (2 years in gerbils) exposure.

Main Results:

• Dexamethasone release was reliably controlled throughout the study periods (>3 years in vitro, 2 years in vivo).
• Diffusional mass transport and drug solubility within the silicone matrix were identified as key factors governing release.
• No significant swelling or shrinking of the implants was observed in vitro or in vivo.

Conclusions:

• Silicone-based cochlear implants demonstrate reliable long-term dexamethasone release, supporting their potential for hearing loss treatment.
• A simplified mathematical model can aid in predicting long-term drug release rates, facilitating implant design and optimization.
• Understanding drug diffusion and solubility is critical for developing advanced, long-duration drug delivery systems.