Center for Hearing and Communication Research, Department of Clinical Neuroscience, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Eur J Pharm Sci. 2010 Jan 31;39(1-3):110-5. doi: 10.1016/j.ejps.2009.11.003. Epub 2009 Nov 18.
Development of efficient local delivery systems for the auditory organ has an important role in clinical practice for the management of inner ear disorders using pharmacological means. Chitosan, a biodegradable polymer, is a good drug carrier with bioadhesive properties. The aim of this study was to investigate the feasibility of using chitosan to deliver drugs to the inner ear across the round window membrane (RWM). Three structurally different chitosans loaded with a tracer drug, neomycin, were injected into the middle ear cavity of albino guinea pigs (n=35). After 7 days the effect of chitosans and neomycin was compared among the treatment groups. The hearing organ was analysed for hair cell loss and the RWM evaluated in term of thickness. All tested chitosan formulations successfully released the loaded neomycin which then diffused across the RWM, and exerted ototoxic effect on the cochlear hair cells in a degree depending on the concentrations used. Chitosans per se had no noxious effect on the cochlear hair cells. It is concluded that the chitosans, and especially glycosylated derivative, are safe and effective carriers for inner ear therapy.
开发用于听觉器官的高效局部递送系统对于使用药理学手段治疗内耳疾病的临床实践具有重要作用。壳聚糖是一种可生物降解的聚合物,具有生物粘附特性,是一种很好的药物载体。本研究旨在探讨壳聚糖通过圆窗膜(RWM)将药物递送至内耳的可行性。将三种结构不同的壳聚糖与示踪药物新霉素一起注入白化豚鼠的中耳腔(n=35)。7 天后,比较了各组壳聚糖和新霉素的作用。分析听觉器官的毛细胞损失,并根据厚度评估 RWM。所有测试的壳聚糖制剂都成功地释放了负载的新霉素,然后新霉素通过 RWM 扩散,并根据使用的浓度对耳蜗毛细胞产生耳毒性作用。壳聚糖本身对耳蜗毛细胞没有毒害作用。因此,壳聚糖,特别是糖基化衍生物,是内耳治疗的安全有效的载体。