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

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.

Formant frequency discrimination with a fine structure sound coding strategy for cochlear implants.

Recent sound coding strategies for cochlear implants (CI) have focused on the transmission of temporal fine structure to the CI recipient. To date, knowledge about the effects of fine structure coding in electrical hearing is poorly charactarized. The aim of this study was to examine whether the presence of temporal fine structure coding affects how the CI recipient perceives sound. This was done by comparing two sound coding strategies with different temporal fine structure coverage in a longitudinal cross-over setting. The more recent FS4 coding strategy provides fine structure coding on typically four apical stimulation channels compared to FSP with usually one or two fine structure channels. 34 adult CI patients with a minimum CI experience of one year were included. All subjects were fitted according to clinical routine and used both coding strategies for three months in a randomized sequence. Formant frequency discrimination thresholds (FFDT) were measured to assess the ability to resolve timbre information. Further outcome measures included a monosyllables test in quiet and the speech reception threshold of an adaptive matrix sentence test in noise (Oldenburger sentence test). In addition, the subjective sound quality was assessed using visual analogue scales and a sound quality questionnaire after each three months period. The extended fine structure range of FS4 yields FFDT similar to FSP for formants occurring in the frequency range only covered by FS4. There is a significant interaction (p = 0.048) between the extent of fine structure coverage in FSP and the improvement in FFDT in favour of FS4 for these stimuli. FS4 Speech perception in noise and quiet was similar with both coding strategies. Sound quality was rated heterogeneously showing that both strategies represent valuable options for CI fitting to allow for best possible individual optimization.