Towards the optimization of drug delivery to the cochlear apex: Influence of polymer and drug selection in biodegradable intracochlear implants

Abstract

There is growing need for new drug delivery systems for intracochlear application of drugs to effectively treat inner ear disorders. In this study, we describe the development and characterization of biodegradable, triamcinolone-loaded implants based on poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol–poly(lactic-co-glycolic acid) (PEG-PLGA) respectively, prepared by hot-melt extrusion. PEG 1500 was used as a plasticizer to improve flexibility and accelerate drug release. The sterilization process was performed by electron beam irradiation, resulting in minimal but acceptable polymer degradation for PEG-PLGA implants. The implants have been characterized by texture analysis, differential scanning calorimetry and X-ray powder diffraction. Compared to PLGA implants, PEG-PLGA implants offer similar flexibility but with improved mechanical stability, which will ease the handling and intracochlear application. A controlled release over three months was observed for dexamethasone and triamcinolone extrudates (drug load of 10%) with similar release profiles for both drugs. PEG-PLGA implants showed an initial slow release rate over several days regardless of the amount of PEG added. Mathematical simulations of the pharmacokinetics of the inner ear based on the in vitro release kinetics indicate a complete distribution of triamcinolone in the whole human scala tympani, which underlines the high potential of the developed formulation.