在梅尼埃病（MD）的治疗中，如何实现中药药效成分在病灶部位选择性地分布，并有针对性地释药，既能有效控制症状，又能尽量减少毒副作用、保护听力，已成为一个亟待解决的关键问题。为此，本项目在前期研究基础上，利用MD病发时活性氧（ROS）水平增加的病理特点以及前庭部位受体的介导作用，构建兼具ROS响应与内耳前庭靶向功能的中药多成分智能化纳米递药系统。该系统同时包载药对丹参-三七多种有效组分，以壳聚糖为氧化响应材料，采用前庭两种受体的共同配体钙离子修饰，不仅可将药物靶向输送至病灶部位，发挥中药多成分协同治疗作用，而且药物能根据ROS水平自动调节释放，从而实现体内定位递送与智能释药一体化。项目通过体外与体内试验，在细胞、组织和动物水平上多层次考察该递药系统的氧化响应释药机理、体内外转运与靶向分布机制、生物相容性及药效学规律，探讨其作为中药多成分内耳给药载体的潜力，为中药制剂的设计理论和方法提供参考。

In the treatment of Meniere's disease (MD), how to achieve selective distribution in the pathogenic site and targeted release of traditional Chinese medicine (TCM) in order to simultaneously control the MD and minimize the side effects and hearing loss, has become an urgent problem to be solved. There exists an increase of reactive oxygen species (ROS) in the inner ear while MD happens. The high expression of the two receptors of cubilin and megalin is found in dark cells of the utricle and those flanking the crista ampullaris of the semicircular canals in the vestibular apparatus. On the basis of the pathological and structural characteristics, as well as our previous research findings, we will perform a novel and innovative study on an intelligent nanoparticulate drug delivery system loaded with TCM multiple components, which possesses ROS-responsive and vestibule-targeted dual functions. Chitosan, an oxidation-responsive material, will be used to formulate the nanoparticles (NPs). And the NPs will be modified by calcium ion, which is common ligand of both receptors co-localized in the vestibular apparatus. Acting as TCM partner, salviae miltiorrhizae and panax notoginseng are going to be employed as model drugs and their effective components including salvianolic acid and panax notoginseng saponins will be loaded in the NPs. The formulated nano-drug delivery system could obtain integrated achievements with in vivo orientated delivery and intelligent release. The encapsulated compound drugs could not only target the pathogenic site and yield multi-component synergistic therapeutic effect, but also automatically release from NPs in feedback ROS concentrations. We will variously examine oxidation-responsive release law, in vivo / in vitro transporting and targeting mechanism, biocompatibility and pharmacodynamics by means of in vitro experimental model, vestibular organotypic cultures and in vivo experiments with the cell, organism and animal level. The experimental results would show the influence of NPs properties on vestibular cellular uptake, membrane permeation and in vivo distribution and demonstrate the potential of the intelligent nanoparticulate drug delivery system serverved as TCM multicomponent delivery carrier via inner ear administration. In conclusion, this study will supply scientific information for developing design theory and methods of TCM preparation.