Biotechnological Effects of Advanced Smart‐Bile Acid Cyclodextrin‐Based Nanogels for Ear Delivery and Treatment of Hearing Loss

Abstract Inner ear delivery requires safe and effective drug delivery vehicles incorporating high‐viscosity formulations with permeation enhancers. This study designs novel thermoresponsive‐smart polymer‐bile acid and cyclodextrin‐based nanogels for inner ear delivery. Nanogels are examined for their rheological and physical properties. The biocompatibility studies will be assessed on auditory and macrophage cell lines by investigating the impact of nanogels on cellular viability, mitochondrial respiration, glycolysis, intracellular oxidative stress, inflammatory profile, and macrophage polarization. Novel ther nanogels based on bile acid and beta‐cyclodextrin show preserved porous nanogels' inner structure, exhibit non‐Newtonian, shear‐thinning fluid behavior, have fast gelation at 37 °C and minimal albumin adsorption on the surface. The nanogels have minimal impact on cellular viability, mitochondrial respiration, glycolysis, intracellular oxidative stress, and inflammatory profile of the auditory cell line House Ear Institute‐Organ of Corti 1 after 24 h incubation. Nanogel exposure of 24 h to macrophage cell line RAW264.7 leads to decreased viability, mitochondrial dysfunction, and increased intracellular ROS and inflammatory cytokines. However, polarization changes from M2 anti‐inflammatory to M1 pro‐inflammatory macrophages are minimal, and inflammatory products of RAW264.7 macrophages do not overly disrupt the survivability of HEI‐OC1 cells. Based on these results, thermoresponsive bile acid and cyclodextrin nanogels can be potential drug delivery vehicles for inner ear drug delivery.