Silver/silver chloride microneedles can detect penetration through the round window membrane.

HYPOTHESIS: Silver-plated microneedles can be used to confirm penetration of semi-permeable membranes such as the round window membrane (RWM) by detection of voltage change at the moment of perforation. BACKGROUND: The introduction of microperforations in the RWM can significantly enhance intracochlear delivery of therapeutics. However, the moment of needle penetration through the RWM cannot be reliably detected by visualization or sensation alone. We explore the ability of electrochemical detection of penetration in defining the precise instant a microneedle enters the inner ear. METHODS: 0.2 mm diameter stainless steel Minutien pins were electroplated with copper, then silver. Pins were then soaked in bleach for 24 h to complete Ag/AgCl plating. Experiments were performed using a 3 mL Franz cell diffusion system with 1%, 2%, 3%, 4%, and 5% saline solution in the donor chamber and artificial perilymph solution in the receptor chamber separated by 5-µm pore synthetic membrane. Continuous voltage measurements were made throughout the process of membrane penetration by the microneedle (N = 6 for each saline concentration). RESULTS: Silver-plated needles were able to detect an instantaneous change in voltage when traversing the membrane from saline solution into artificial perilymph. As calculated, the magnitude of the change in voltage upon penetration increased with increasing saline concentration and was stable across trials. CONCLUSION: Ag/AgCl coated microneedles are effective in detecting the moment of penetration across semi-permeable membranes. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 307-311, 2017.

Microperforations significantly enhance diffusion across round window membrane.

HYPOTHESIS: Introduction of microperforations in round window membrane (RWM) will allow reliable and predictable intracochlear delivery of pharmaceutical, molecular, or cellular therapeutic agents. BACKGROUND: Reliable delivery of medications into the inner ear remains a formidable challenge. The RWM is an attractive target for intracochlear delivery. However, simple diffusion across intact RWM is limited by what material can be delivered, size of material to be delivered, difficulty with precise dosing, timing, and precision of delivery over time. Further, absence of reliable methods for measuring diffusion across RWM in vitro is a significant experimental impediment. METHODS: A novel model for measuring diffusion across guinea pig RWM, with and without microperforation, was developed and tested: cochleae, sparing the RWM, were embedded in 3D-printed acrylic holders using hybrid dental composite and light cured to adapt the round window niche to 3 ml Franz diffusion cells. Perforations were created with 12.5-µm-diameter needles and examined with light microscopy. Diffusion of 1 mM Rhodamine B across RWM in static diffusion cells was measured via fluorescence microscopy. RESULTS: The diffusion cell apparatus provided reliable and replicable measurements of diffusion across RWM. The permeability of Rhodamine B across intact RWM was 5.1 × 10(9-) m/s. Manual application of microperforation with a 12.5-µm-diameter tip produced an elliptical tear removing 0.22 ± 0.07% of the membrane and was associated with a 35× enhancement in diffusion (P < 0.05). CONCLUSION: Diffusion cells can be applied to the study of RWM permeability in vitro. Microperforation in RWM is an effective means of increasing diffusion across the RWM.