递药系统在重大疾病治疗方面有着普通制剂无可比拟的优势，但体内诸多不同性质生理屏障对其高效传递存在极大影响，导致目标器官导入率低。申请者瞄准上述瓶颈问题，对递药系统构建与机制进行研究，取得系列原创性成果。1、实现多个口服新靶点递药，发现“粘液和上皮细胞屏障对递药系统构建存在矛盾”，原创功能性递药系统，显著提高生物大分子药物跨膜吸收；2、创新性构建肿瘤微环境程序响应、级联靶向定位释药系统，突破肿瘤亚细胞递药多重生理屏障；3、实现十二指肠定位释药，解决该部位短、药物难以定位作用的难题。近五年以通讯作者在本领域重要期刊ACS Nano, Adv. Funct. Mater., Angew. Chem. Int. Ed.等发表SCI文章32篇，4篇影响因子大于10；五年内累计他引569次。担任药剂学权威期刊Mol. Pharm.客座编辑。获教育部新世纪优秀人才支持计划和中国药学会青年药剂学奖。

Drug delivery systems have shown tremendous superiority when compared with traditional formulations in the treatment of critical diseases. However, their efficacy is greatly challenged by the in vivo ubiquitous physiological barriers, which profoundly compromise their selectivity and targetability. In the aim to overcome the organic and cellular barriers in vivo, the applicant has constructed a series of efficient drug delivery systems, evaluated their mechanism of actions, and successfully obtained the following significant breakthroughs. 1. Discovering and realizing new targeted sites in intestinal epithelial cells, demonstrating for the first time "the mucus permeation and epithelial absorption require very different surface properties of a nanocarrier", originally designing nanomedicinal systems that simultaneously overcome both barriers of epithelial cells and mucus, thus promoting the oral absorption of protein and peptide drugs. 2. Creatively establishing multistage stimulus-responsive drug delivery systems for programmed and cascade sub-cellular targeting to overcome the tumor subcellular barriers. 3. For the first time achieving duodenum-specific drug release for sustained effect regardless of the fact that length of duodenum is short. Hence, through the above-mentioned studies, the applicant is trying to promote the application of drug delivery system for the treatment of different diseases by seeking the effective solutions to the bottleneck problems in the in vivo drug delivery. During recent 5 years, the applicant has published 32 SCI papers as corresponding author in top journal of our field such as ACS Nano, Adv. Funct. Mater., Angew. Chem. Int. Ed., etc. Among them, 4 papers have the impact factor higher than 10. The total non-self citing number in recent 5 years of all papers is 569. Also the applicant has been invited as the guest editor of the authorative journal of Mol. Pharm. The research achievement has gained Excellent Talents Supporting programs for New Century and the first session of the China Pharmaceutical Association Youth pharmacy Prize.