The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia.
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, 21101, Serbia.
Adv Healthc Mater. 2024 Jun;13(16):e2303149. doi: 10.1002/adhm.202303149. Epub 2024 Mar 28.
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.
内耳给药需要安全有效的药物输送载体，将高粘度制剂与渗透增强剂结合使用。本研究设计了新型温敏智能聚合物-胆酸和环糊精纳米凝胶用于内耳给药。考察了纳米凝胶的流变学和物理性质。通过研究纳米凝胶对细胞活力、线粒体呼吸、糖酵解、细胞内氧化应激、炎症谱和巨噬细胞极化的影响，评估其在听觉和巨噬细胞系中的生物相容性。新型胆酸和β-环糊精基温敏纳米凝胶保持了多孔纳米凝胶的内部结构，表现出非牛顿、剪切稀化流体行为，在 37°C 时快速凝胶化，表面白蛋白吸附最小。纳米凝胶孵育 24 小时后，对 HEI-OC1 细胞系的细胞活力、线粒体呼吸、糖酵解、细胞内氧化应激和炎症谱几乎没有影响。纳米凝胶暴露于 RAW264.7 巨噬细胞系 24 小时会导致细胞活力降低、线粒体功能障碍以及细胞内 ROS 和炎症细胞因子增加。然而，从抗炎 M2 型到促炎 M1 型巨噬细胞的极化变化很小，并且 RAW264.7 巨噬细胞的炎症产物不会过度破坏 HEI-OC1 细胞的存活率。基于这些结果，温敏胆酸和环糊精纳米凝胶可以成为内耳药物输送的潜在药物输送载体。
