目前可供主动靶向纳米粒选择的靶点种类较少，而机体内存在着许多决定药物体内动态的药物转运体，例如新型有机阳离子转运体2(OCTN2)是L-肉毒碱吸收的主要载体。转运体介导靶向纳米粒的研究现在仍处于探索初期，尚待深入研究。为了丰富纳米粒的靶点选择范围和解析转运体与受体作为靶点的差别，本项目以肠道上皮细胞顶侧OCTN2为靶点，构建系列L-肉毒碱衍生物修饰的主动靶向纳米粒。在包裹增溶难溶性药物紫杉醇的同时，靶向纳米粒还具有与肠细胞的高度亲和性和内吞力，提高膜转运，降低首过效应等优势。本研究从细胞、组织和动物水平对靶向纳米粒进行制剂学、生物学、药动学和药效学评价，建立纳米结构/组成与其细胞结合/摄取和膜渗透性的定量关系，解析靶向纳米粒高吸收性的关键制剂学性质，重点从蛋白和基因水平、纳米粒内化机制和转运体的膜转运特征等多角度解析对OCTN2的调控机制，为后续转运体－纳米粒体系的研究提供理论和技术支撑。

Currently, there are few available targets for active targeting nanoparticles. However, the body has a lot of transporters in determining the drug disposition's fate, such as novel organic cation transporter 2(OCTN2)，which is the main absorption carrier of L-carnitine. Transporter-mediated targeting nanoparticles are still at the initial stage and need to be studied. In order to increase the target types of nanoparticles and to elucidate the target difference between transporter and receptor, L-carnitine derivatives modified nanoparticles are developed to target OCTN2 transporter on the apical side of enterocytes. When encapsulating and solubilizing insoluble drug paclitaxel, active targeting nanoparticles also have bioadhesion, membrane permeation and reduce first-pass effect. Physicochemical, biological, pharmacokinetic and pharmacodynamic propeties of OCTN2 targeting nanoparticles are studied from the cell level, the organization level and the whole animal level. And then the quantitative relationships between nanoparticle structure and cellular binding/uptake and memrbane permeability, are estabilished to elucidate the key pharmaceutical mechanism of enhanced oral absorption of nanoparticles. Sepcial emphasis is put on studying regulation mechanism of OCTN2 activity from protein and gene level, endocytosis pathway of nanoparticles and transporting charactersitic of transporter, which would provide support for the research and development of the transporter-mediated targeting nanoparticles.