Department of Chemical & Biological Engineering, Korea National University of Transportation, Chungju 380-702, Republic of Korea.
J Control Release. 2013 Aug 28;170(1):74-82. doi: 10.1016/j.jconrel.2013.04.024. Epub 2013 May 9.
We have synthesized taurocholic acid (TCA) linked heparin-docetaxel (DTX) conjugates for oral delivery of anticancer drug. The ternary biomolecular conjugates formed self-assembly nanoparticles where docetaxel was located inside the core and taurocholic acid was located on the surface of the nanoparticles. The coupled taurocholic acid in the nanoparticles had enhanced oral absorption, presumably through the stimulation of a bile acid transporter of the small intestine. The oral absorption profile demonstrated that the concentration of the conjugates in plasma is about 6 fold higher than heparin alone. An anti-tumor study in MDA-MB231 and KB tumor bearing mice showed significant tumor growth inhibition activity by the ternary biomolecular conjugates. Ki-67 histology study also showed evidence of anticancer activity of the nanoparticles. Finally, noninvasive imaging using a Kodak Molecular Imaging System demonstrated that the nanoparticles were accumulated efficiently in tumors. Thus, this approach for oral delivery using taurocholic acid in the ternary biomolecular conjugates is promising for treatment of various types of cancer.
我们合成了牛磺胆酸（TCA）连接的肝素-多西紫杉醇（DTX）缀合物，用于抗癌药物的口服给药。形成的三元生物分子缀合物自组装成纳米颗粒，其中多西紫杉醇位于核心内部，牛磺胆酸位于纳米颗粒的表面。纳米颗粒中结合的牛磺胆酸通过刺激小肠中的胆汁酸转运体增强了口服吸收，口服吸收曲线表明，与肝素相比，缀合物在血浆中的浓度约高 6 倍。在 MDA-MB231 和 KB 荷瘤小鼠中的抗肿瘤研究表明，三元生物分子缀合物具有显著的肿瘤生长抑制活性。Ki-67 组织学研究也表明纳米颗粒具有抗癌活性。最后，使用柯达分子成像系统进行的非侵入性成像表明，纳米颗粒在肿瘤中有效积累。因此，使用三元生物分子缀合物中的牛磺胆酸进行口服给药的方法有望用于治疗各种类型的癌症。
