基于微流控芯片技术的复方脂质体-TAT/TD生物促透给药系统的构建及作用机制研究——以藏药白脉软膏为例

构建体现整体功效的新型给药系统是突破制约中药制剂现代化发展重要瓶颈问题的途径之一。申请人前期研究白脉软膏发现其通过多成分、多途径、多靶点治疗骨关节炎，但原粉入药制成乳膏的制剂方式严重影响其疗效、质量稳定性、安全性及深层渗透性，是研究本项目关键科学问题的理想模型药物。因此，本项目拟将白脉软膏处方中饮片水提精制和提取挥发油，提取物采用微流控技术制备脂质体，借助穿透肽TAT修饰、促渗肽TD协同技术，将脂质体输送至皮肤深层，当脂质体与皮肤融合后高效促进药物渗透入组织深部，形成更适宜于复杂体系的TAT/TD生物联合促透-复方脂质体给药系统；利用药动学和药效学等方法探索其有效提高药物经皮渗透性和生物利用度的作用机制，围绕TNF、NF-κB和HIF-1信号通路阐释新型给药系统调控炎症、软骨和血管新生治疗骨关节炎的作用机制，为研究现代中药外用复方制剂提供科学思路，丰富传统医学的科学内涵。

It is one of the ways to break through the important bottleneck of the modernization of Traditional Chinese Medicine preparation to construct a new drug delivery system which embodies the general efficacy. The applicant's previous study on Baimai Ointment found that it treated osteoarthritis through multi-components, multi-targets and multi-pathways. However, the preparation method of making ointment from raw powder seriously affects its full function, the quality stability, safety and deep permeability. It is an ideal model drug to study the key scientific issues of this project...In this study, liposomes are prepared from the water extraction and volatile oil of Baimai ointment by microfluidics. The liposomes are modified by penetrating peptide TAT and combined with pro-osmotic peptide TD to transport the liposomes to the deep layer of skin. When the liposomes fuse into the skin, transdermal peptide TD will further penetrate them into the issues in coordination with other drugs. Thus, to form a TAT/TD liposome transdermal delivery system that is more suitable for the complex system. Then, pharmacokinetic and Pharmacodynamics methods were used to study the mechanism of its effective improvement of drug transdermal permeability and bioavailability. Focusing on the TNF signaling pathway, NF-κB signaling pathway and HIF-1 signaling pathway, the mechanism of the novel administration system regulating inflammation, cartilage and angiogenesis in the treatment of osteoarthritis was elucidated. ..To provide scientific thought for the study of TCM compound topical formulations and enrich the scientific connotation of traditional medicine.