Key Laboratory of Chemical Engineering Process & Technology for High-efficiency Conversion, College of Heilongjiang Province, School of Chemistry and Material Science, Heilongjiang University, Harbin 150080, China.
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, Heilongjiang Province, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China.
Int J Mol Sci. 2018 Oct 12;19(10):3132. doi: 10.3390/ijms19103132.
The present investigation aimed to develop a tumor-targeting drug delivery system for paclitaxel (PTX). The hydrophobic deoxycholic acid (DA) and active targeting ligand folic acid (FA) were used to modify water-soluble chitosan (CS). As an amphiphilic polymer, the conjugate FA-CS-DA was synthesized and characterized by Proton nuclear magnetic resonance (¹H-NMR) and Fourier-transform infrared spectroscopy (FTIR) analysis. The degree of substitutions of DA and FA were calculated as 15.8% and 8.0%, respectively. In aqueous medium, the conjugate could self-assemble into micelles with the critical micelle concentration of 6.6 × 10 mg/mL. Under a transmission electron microscope (TEM), the PTX-loaded micelles exhibited a spherical shape. The particle size determined by dynamic light scattering was 126 nm, and the zeta potential was +19.3 mV. The drug loading efficiency and entrapment efficiency were 9.1% and 81.2%, respectively. X-Ray Diffraction (XRD) analysis showed that the PTX was encapsulated in the micelles in a molecular or amorphous state. In vitro and in vivo antitumor evaluations demonstrated the excellent antitumor activity of PTX-loaded micelles. It was suggested that FA-CS-DA was a safe and effective carrier for the intravenous delivery of paclitaxel.
本研究旨在开发一种用于紫杉醇（PTX）的肿瘤靶向药物传递系统。疏水性去氧胆酸（DA）和活性靶向配体叶酸（FA）被用于修饰水溶性壳聚糖（CS）。作为一种两亲性聚合物，FA-CS-DA 缀合物通过质子核磁共振（¹H-NMR）和傅里叶变换红外光谱（FTIR）分析进行了合成和表征。DA 和 FA 的取代度分别计算为 15.8%和 8.0%。在水介质中，该缀合物可以自组装成胶束，临界胶束浓度为 6.6×10mg/mL。在透射电子显微镜（TEM）下，负载 PTX 的胶束呈现出球形。动态光散射法测定的粒径为 126nm，zeta 电位为+19.3mV。载药效率和包封效率分别为 9.1%和 81.2%。X 射线衍射（XRD）分析表明，PTX 以分子或无定形状态包封在胶束中。体外和体内抗肿瘤评价表明，负载 PTX 的胶束具有优异的抗肿瘤活性。因此，FA-CS-DA 是一种安全有效的紫杉醇静脉传递载体。
