血-内耳屏障和血脑屏障限制了中药疗效的发挥。内耳（局部）给药能避开上述两种屏障的阻碍，将药物有效递送至内耳及脑。已完成的国家自然科学基金研究表明中药多组分采用内耳给药可经圆窗膜分布至内耳和脑，将其包载于纳米粒中可进一步改善递释效果，但也发现了普通纳米粒作为内耳给药载体的不足。"质量源于设计"，本项目拟在此基础上，从剂型角度深入研究，并提高研究层面，应用体外圆窗膜模型、体外培养耳蜗模型和豚鼠体内试验，在细胞、器官和动物水平上多层次考察纳米粒特性对耳蜗细胞摄取、经膜渗透、体内转运的影响及与分布的关系，筛选适宜的纳米系统；以药对丹参-三七有效组分为模型，深入探索纳米传递系统及与原位凝胶结合制成的双相释药系统，作为复方多组分内耳给药载体的潜力，考察其递药机制。结合前期研究，构建比较系统的中药复方内耳给药系统的理论体系，丰富中药制剂的研究内容，为中药进入内耳或脑内充分发挥治疗作用奠定基础。

Drug delivery of traditional Chinese medicine (TCM) into the inner ear and the brain is made difficult by the presence of the blood-inner ear barrier(BIB) and blood-brain barrier(BBB). There is an increasing interest in the treatment of inner ear disorders or brain diseases by topical application of drugs to the inner ear. It's expected to be a breakthrough, which can bypass BIB and BBB.One of the most important issues to overcome before full clinical application is the development of smart delivery systems for drugs to the target sites and controlled release in the inner ear and the brain. The research of completed NSFC（30801553）showed that the effective components of TCM diffused through the round window membrane (RWM) into the perilymph in the inner ear and then transported to the cerebrospinal fluid (CSF) bypassing the BBB, and introcochlear administration could greatly improve drug distribution within the inner ear and the brain. Furthermore, nanoparticles(NP) which substantially increased local bioavailability, had significant sustained-release effect. Drugs or NP in the perilymphatic compartment might transport through the cochlear aqueduct and into CSF. However, NP also displayed the shortage as drugs carrier via inner ear administration. Derived from quality by design (QbD) and its experimental design, it needs further research for the formulations from more aspects in the present study. We will examine the properties of NP by means of in vitro experimental model for RWM, cochlear cultures and in vivo experiments of guinea pigs, with the cell, organism and animal level. Further, we will show the influence for cochlear cellular uptake, membrane permeation capacity and drug delivery in vivo, and the relationship between the properties of NP and distribution as well, and screen the appropriate nano-drug delivery system. Acting as TCM partner, salviae miltiorrhizae and panax notoginseng are going to be selected as model drugs. Nano- and biphasic drug delivery systems will be explored the capacity as introcochlear drug carriers loaded with the TCM partner, especially the transport mechanism through RWM. Based on our previous research, this study will open up a new research field on inner ear drug delivery system of TCM compound prescription and construct its theory. Besides, the study will supply scientific information for developing compound preparation of TCM and establish the foundation of exerting its therapeutic effect for TCM into the inner ear and the brain.