Intracochlear PLGA based implants for dexamethasone release: Challenges and solutions

Graphical abstract

Abstract

The effective treatment of diseases of the inner ear is currently an unmet medical need. Local controlled drug delivery to the cochlea is challenging due to the hidden location, small volume and high sensitivity of this organ. A local intracochlear delivery of drugs would avoid the problems of intratympanic (extracochlear) drug application, but is more invasive. The requirements for such a delivery system include a small size and appropriate flexibility. The delivery device must be rigid enough for surgical handling but also flexible to avoid traumatizing cochlear structures. We developed biodegradable dexamethasone loaded PLGA extrudates for the controlled intracochlear release. In order to achieve the desired flexibility, Polyethylene glycol (PEG) was used as a plasticizer. In addition to the drug release, the extrudates were characterized in vitro by differential scanning calorimetry (DSC) and texture analysis. Simulation of the pharmacokinetics of the inner ear support the expectation that a constant perilymph drug level is obtained after few hours and retained over several weeks. Ex vivo implantation of the extrudates into a guinea pig cochlea indicate that PEG containing extrudates have the desired balance between mechanical strength and flexibility for direct implantation into the cochlea. The location of the implant was visualized by computer tomography. In summary, we postulate that intracochlear administration of drug releasing biodegradable implants is a new and promising approach to achieve local drug delivery to the cochlea for an extended time.