Predictability of drug release from cochlear implants.

A simplified mathematical theory is presented allowing for in silico simulation of the effects of key parameters of miniaturized implants (size and composition) on the resulting drug release kinetics. Such devices offer a great potential, especially for local drug treatments, e.g. of the inner ear. However, the preparation and characterization of these systems is highly challenging, due to the small system dimensions. The presented mathematical theory is based on Fick's second law of diffusion. Importantly, theoretical predictions do not require the knowledge of many system-specific parameters: Only the "apparent" diffusion coefficient of the drug within the implant matrix is needed. This parameter can be easily determined via drug release measurements from thin, macroscopic films. The validity of the theoretical model predictions was evaluated by comparison with experimental results obtained with a cochlear implant. The latter consisted of miniaturized electrodes, which were embedded in a silicone matrix loaded with various amounts of dexamethasone. Importantly, independent experimental results confirmed the theoretical predictions. Thus, the presented simplified theory can help to significantly speed up the optimization of this type of controlled drug delivery systems, especially if long release periods are targeted (e.g., several months or years). Straightforward experiments with thin, macroscopic films and computer simulations can allow for rapid identification of optimal system design.