中药中脂溶性药效成分普遍存在着溶解性差、口服生物利用度低的问题。穿心莲的药效组分二萜内酯类成分就是其中的一类典型代表，严重影响其临床疗效的发挥。胶束具备改善难溶性中药组分的药动学性质而提高口服吸收的优势，但胶束口服吸收仍受三大屏障（胃肠道稳定性、粘液渗透性和跨膜转运效率）的限制。为克服胶束口服吸收屏障、更高效地改善脂溶性成分的口服吸收，本课题以穿心莲二萜内酯组分为模型药物，构建pH依赖、易粘液渗透和寡肽转运蛋白（PEPT-1）靶向的“三位一体”智能化胶束-微粒系统。该系统在小肠溶蚀释放胶束，以完整的胶束形态渗透粘液层，靶向肠上皮细胞而提高跨膜转运效率，进入血液循环而发挥药效。课题综合运用药剂学、药动学和分子生物学等技术手段，在细胞-组织-动物水平上，系统评价胶束的靶向性与跨膜转运机制，阐明微粒的释放规律、体内吸收过程及提高药效作用的机制。以期为提升难溶性中药组分口服生物利用度开辟新的途径。

Poor water solubility and low oral bioavailability are challenges in fat-soluble effective components in Chinese traditional medicines, and seriously limit clinical effects. Andrographis diterpene lactone, the main active components separated from Andrographis paniculata, is one of the typical representative. Polymeric micelles are adopted to increase oral absorption efficiency of insoluble components of traditional Chinese medicine by improving pharmacokinetic properties, but are still subjected to three oral absorption barriers which are stability in gastrointestinal tract, mucus permeability and transmembrane transport efficiency, respectively. To overcome oral absorption barriers of micelles and more efficiently improve the oral absorption of liposoluble components, a pH-dependent, easily mucus penetration and oligopeptide transporters (PEPT-1) targeted trinity-intelligent micelle – microparticle system is prepared with andrographis diterpene lactone as model drugs. This system dissolves and releases micelles in intestine, then complete micelles are easy to penetrate mucus and targeted transport across intestinal epithelia cells, ultimately to enter blood circulation and exert pharmacological efficacy. Pharmaceutics, pharmacokinetics and molecular biology are integrated used in this project, to evaluate the mechanism of micellar targeting and transmembrane transport, clarify the release and in vivo absorption process of particles, and study the increment of anti-tumor efficacy mechanism in cells- organization –animal level. In consequence, this project provides promising approaches to promote oral bioavailability of insoluble components of traditional Chinese medicine.