难溶性中药成分的肺吸入给药是中药药剂学研究的难点。如何构筑具备良好的空气动力学粒径且稳定性能好的肺吸入粒子，实现难溶性药物肺部高效给药，是难溶性药物肺吸入给药研究的关键。本课题提出“构建以纳米晶体为载药形态的肺吸入复合粒子，其由一、二级粒子组成。一级粒子为承载纳米晶体粒子的多孔微粒，易于肺部沉积，给药后可水化再分散出二级粒子；二级粒子为PEG化修饰的纳米晶体粒子，可快速穿越肺粘液层屏障，改善难溶性药物溶出与吸收”。为此，本项目创新性地运用纳米晶体技术与喷雾冷冻干燥造粒技术制备以纳米晶体为载药形态的肺吸入复合粒子，运用多粒子追踪等技术探讨纳米晶体表面性质与其肺黏液穿透性能的内在机制，运用玻璃化转变理论与水分活度理论系统阐明影响复合粒子再分散性能的内在规律与稳定化机制，建立以纳米晶体为载药形态的肺吸入复合微粒的粒子化技术方法与稳定化调控策略。本项目将为难溶性中药成分的肺吸入给药提供新的方法。

Pulmonary drug delivery of poorly soluble drug is the difficulty of TCM pharmaceutics. How to design the new inhalable delivery system with the excellent aerodynamic particle size and good stability for the poor soluble ingredients of Chinese medicine, and to improve the pulmonary bioavailability of poorly soluble ingredients of Chinese medicine, become a difficult problem of pulmonary drug delivery. Therefore, we are trying to design the novel inhalable composite microparticle. The inhalable composite microparticles composed of "one-stage particles" and "two-stage particles", "one-stage particles" used as porous carrier particles for nanocrystals (two-stage particles) particles, and easily redispersed into the two-stage particles after inhalation and facilitate lung deposition. And “two-stage particles” as PEGylated nanocrystals of drug and used to improve the dissolution of poorly soluble drug”. Therefore, our group will prepare the inhaled composite particles loading drug nanocrystals by means of nanocrystal technology and spray-freeze-drying technology, and to explore the internal mechanism of the surface properties of nanocrystals related with its mucus penetration by multiparticle tracking technology, and elucidate the stabilization mechanism on dispersion of composite particles using glass transition theory and water activity theory, and obtain the forming technique and control strategy for pulmonary inhaled composite microparticles. This study can provide the novel technology and method for inhalation administration of poorly soluble drug.