To improve the affinity of alginate to the hydrophobic drug molecules, such as ibuprofen, the Ugi four-component condensation reaction involving sodium alginate (SA), tosylmethyl isocyanide, propionaldehyde and octylamine was proposed to synthesize the novel amphiphilic alginate-bisamide derivative (AABD) without any organic solvents and catalysts. The molecular structure and self-aggregate behavior of the resultant AABD was characterized by FT-IR spectrometer, ¹H NMR spectrometer, X-ray diffraction, thermal gravimetric analysis, fluorescence spectrophotometer, transmission electron microscope and dynamic light scattering. Meanwhile, the loading and in vitro release of ibuprofen for the AABD microcapsules prepared by the emulsification method as well as their cytotoxicity were also investigated. Experimental results showed that the AABD with the degree of substitution of 19.41% was successfully prepared by the Ugi reaction, and the grafting of hydrophobic side groups on the backbone of alginate was conducive to enhancing its molecular flexibility and colloidal interface activity. Therefore, the AABD could reveal good amphiphilic property with the critical aggregation concentration (CAC) of 0.105 g/L in 0.15 mol/L aqueous NaCl solution, and form the self-aggregated micelle with the average hydrodynamic diameter of 396 nm (PDI = 0.31) and zeta potential at about − 62.4 mV. Furthermore, the prepared AABD microcapsules displayed the high encapsulation efficiency and sustained-release property in comparison with the SA microcapsules for the good affinity of AABD to hydrophobic ibuprofen that retarded the drug diffusion. And it also exhibited low cytotoxicity to the murine macrophage RAW264.7 cells. Therefore, the novel amphiphilic AABD synthesized by the Ugi reaction would be of great potentials as the hydrophobic drug carriers for sustained-release formulations.

为了提高海藻酸盐对布洛芬等疏水性药物分子的亲和力，提出了涉及海藻酸钠 (SA)、甲苯磺酰甲基异氰化物、丙醛和辛胺的 Ugi 四组分缩合反应，以合成新型两亲性海藻酸盐-双酰胺衍生物 (AABD)不含任何有机溶剂和催化剂。所得 AABD 的分子结构和自聚集行为由 FT-IR 光谱仪表征，¹H NMR 光谱仪、X 射线衍射、热重分析、荧光分光光度计、透射电子显微镜和动态光散射。同时，对乳化法制备的AABD微胶囊中布洛芬的负载量和体外释放情况及其细胞毒性进行了研究。实验结果表明，通过Ugi反应成功制备了取代度为19.41%的AABD，在海藻酸盐骨架上接枝疏水侧基有利于增强其分子柔韧性和胶体界面活性。因此，AABD 在 0.15 mol/L NaCl 水溶液中的临界聚集浓度 (CAC) 为 0.105 g/L，显示出良好的两亲性，并形成平均流体动力学直径为 396 nm (PDI = 0.31) 和 zeta 电位约为 - 62.4 mV 的自聚集胶束。此外，与 SA 微胶囊相比，制备的 AABD 微胶囊显示出高封装效率和缓释特性，因为 AABD 对疏水性布洛芬具有良好的亲和力，从而延缓了药物扩散。并且它还对鼠巨噬细胞 RAW264.7 细胞表现出低细胞毒性。因此，通过 Ugi 反应合成的新型两亲性 AABD 作为缓释制剂的疏水性药物载体具有巨大的潜力。与 SA 微胶囊相比，制备的 AABD 微胶囊显示出高封装效率和缓释特性，因为 AABD 与疏水性布洛芬具有良好的亲和力，从而延缓了药物扩散。并且它还对鼠巨噬细胞 RAW264.7 细胞表现出低细胞毒性。因此，通过 Ugi 反应合成的新型两亲性 AABD 作为缓释制剂的疏水性药物载体具有巨大的潜力。与 SA 微胶囊相比，制备的 AABD 微胶囊显示出高封装效率和缓释特性，因为 AABD 与疏水性布洛芬具有良好的亲和力，从而延缓了药物扩散。并且它还对鼠巨噬细胞 RAW264.7 细胞表现出低细胞毒性。因此，通过 Ugi 反应合成的新型两亲性 AABD 作为缓释制剂的疏水性药物载体具有巨大的潜力。