生物大分子药物高效递释系统（BDDS）的体内递送是其克服多种生理屏障从给药部位转运到药物作用部位的一个关键过程。给药途径不同、药物作用部位不同，BBDS面临的生理屏障亦不同。但现有BBDS体内递送效率不高，且递送机理尚不完全明确。本课题拟针对五类疾病涉及的四类生物大分子药物（蛋白多肽、抗体、核酸和疫苗），以三种途径给药（静脉注射、局部注射和口服）时所需克服的体液屏障（血液屏障、胃肠液屏障）、组织屏障（血-脑屏障、血-眼屏障、胃肠道上皮屏障）为基点，探讨BDDS的表面性质、粒径大小、靶分子修饰及体内过程完整性等理化性质对递送效率的影响，并结合不同生理屏障的微环境和细胞表面的特异性结合位点，采用体内外定量检测和高分辨率成像等技术手段，研究BDDS的结构和性质与屏障细胞亲和性和跨膜转运效率的相关性，系统阐明不同给药途径的BDDS递送机制并建立理论体系，为BDDS优化和产品研发提供科学依据。

The key process for in vivo transportation of biological macromolecular drug delivery system (BDDS) is to overcome a wide variety of physiological barriers. Those barriers are vary according to different routes of administration and different action site. At present, the existing BDDS is in low efficiency and the mechanism remains unclear. This project is to study the influence of the physical properties of BDDS such as surface properties, particle size, target molecule modification and integrity to drug delivery efficiency of BDDS through four types of biological macromolecular drugs (protein peptides, antibodies, nucleic acids, and vaccine), involving five diseases, which fluid barriers (blood barriers, gastric intestinal barrier)and tissure barriers (blood-brain barrier, blood-eye barrier, gastrointestinal epithelial barrier) need to be overcame when giving three different routes administration (intravenous injection, injection and oral administration). In addition, with the combination of microenvironment of different physiological barrier and specific binding sites on the surface of the cells as well as using high techniques (such as quantitative detection and high resolution imaging techniques), the correlation between BDDS (structure and properties) and barrier cells (affinity and transmembrane efficiency) were also studied. The mechanism and theory of BDDS in different means of administration will be systematically illustrated and scientific basis for BDDS optimization and product research and development will also be founded after these study works.