中文摘要
针对皂苷类中药口服吸收差的问题,基于血浆脂蛋白富脂结构的启发,结合植物蛋白--玉米阮优异的生物相容性和特殊的两亲性结构,本项目提出:以三七总皂苷为模型药物;将玉米阮与脂质或类脂材料重组为脂化玉米阮;借助三七总皂苷的表面活性,实现其与脂化玉米阮的超分子共组装;通过超分子独特的纳米结构提高三七总皂苷的口服生物利用度。前期研究显示:基于β-谷甾醇的脂化玉米阮稳定性较好;三七总皂苷被高效负载;其活性成分人参皂苷Rb1在Caco-2单细胞模型上的跨膜转运效率显著增加;口服药效大幅度提高。在此基础上,项目将围绕超分子的组装原理、载药规律和口服吸收机制等展开系统研究,阐释其在提高皂苷类中药口服生物利用度方面的科学性和有效性。本项目将纳米科学和中药学的成果相结合构筑新型仿生纳米口服给药系统,为中药口服载体的研究提供了新思路和实践依据,具有较高的研究价值和潜在的应用前景。
英文摘要
Inspired by the structure of serum lipoprotein and based on the biocompatibility and specific amphiphilic structure of Zein (a plant protein), we propose research idea of this project as follows to improve the oral absorption of low permeable drugs. Here notoginseng total saponins (NTS) were choosing as model drug, a lipidation Zein (Lipozein) was prepared by thermal recombination of Zein and lipids. By means of NTS’s surface activity, NTS could assemble into nano structure of Lipozein to form NTS- Lipozein supramolecular. This formed nano supramolecular can promote significantly NTS’s oral absorption owing to their special nanoparticle sizes and riched lipid structure. Preliminary studies indicated that stable NTS- Lipozein could be formed by a certain proportion of Zein and β-Sitosterol. And the formed Lipozein has favorable drug capacity of NTS, as well as higher transport rate of Rb1 across Caco-2 cells. This project will be focused on the regular pattern of Zein and lipids combination, assembly rules, microstructures, mechanism of absorption enhancement for GIT and bioavailability in vivo with the aid of the technology of fluorescent quenching in water etc. Furthermore the applicability of this Lipozein will also be explored to improve the oral bioavailability of the NTS analogues. Thus project will construct a novel biomimic lipoprotein nanocarrier by integration of the achievements of nano science and traditional Chinese medicine, provides high research value and potential application prospect because it will give us new strategy and practice foundation for enriching oral absorption technology of traditional Chinese medicine.
