On account of the rigid structure of alginate chains, the oxidation-reductive amination reaction was performed to synthesize the reductive amination of oxidized alginate derivative (RAOA) that was systematically characterized for the development of pharmaceutical formulations. The molecular structure and self-assembly behavior of the resultant RAOA was evaluated by an FT-IR spectrometer, a ¹H NMR spectrometer, X-ray diffraction (XRD), thermal gravimetric analysis (TGA), a fluorescence spectrophotometer, rheology, a transmission electron microscope (TEM) and dynamic light scattering (DLS). In addition, the loading and in vitro release of ibuprofen for the RAOA microcapsules prepared by the high-speed shearing method, and the cytotoxicity of the RAOA microcapsules against the murine macrophage RAW264.7 cell were also studied. The experimental results indicated that the hydrophobic octylamine was successfully grafted onto the alginate backbone through the oxidation-reductive amination reaction, which destroyed the intramolecular hydrogen bond of the raw sodium alginate (SA), thereby enhancing its molecular flexibility to achieve the self-assembly performance of RAOA. Consequently, the synthesized RAOA displayed good amphiphilic properties with a critical aggregation concentration (CAC) of 0.43 g/L in NaCl solution, which was significantly lower than that of SA, and formed regular self-assembled micelles with an average hydrodynamic diameter of 277 nm (PDI = 0.19) and a zeta potential of about −69.8 mV. Meanwhile, the drug-loaded RAOA microcapsules had a relatively high encapsulation efficiency (EE) of 87.6 % and good sustained-release properties in comparison to the drug-loaded SA aggregates, indicating the good affinity of RAOA to hydrophobic ibuprofen. The swelling and degradation of RAOA microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen. Moreover, it also displayed low cytotoxicity against the RAW264.7 cell, similar to the SA aggregates. In view of the excellent advantages of RAOA, it is expected to become the ideal candidate for hydrophobic drug delivery in the biomedical field.

中文翻译：

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用于疏水给药的氧化海藻酸盐衍生物还原胺化的分子结构和自组装行为

由于海藻酸盐链的刚性结构，进行氧化-还原胺化反应以合成氧化海藻酸盐衍生物（RAOA）的还原胺化，其系统地表征用于药物制剂的开发。所得 RAOA 的分子结构和自组装行为由 FT-IR 光谱仪评估，¹H NMR 光谱仪、X 射线衍射 (XRD)、热重分析 (TGA)、荧光分光光度计、流变学、透射电子显微镜 (TEM) 和动态光散射 (DLS)。此外，还研究了高速剪切法制备的RAOA微胶囊布洛芬的负载和体外释放，以及RAOA微胶囊对鼠巨噬细胞RAW264.7细胞的细胞毒性。实验结果表明，疏水性辛胺通过氧化还原胺化反应成功接枝到海藻酸盐骨架上，破坏了原料海藻酸钠（SA）的分子内氢键，从而增强了其分子灵活性，实现了自组装性能RAOA。最后，合成的 RAOA 显示出良好的两亲性，在 NaCl 溶液中的临界聚集浓度 (CAC) 为 0.43 g/L，明显低于 SA，并形成了平均流体动力学直径为 277 nm (PDI) 的规则自组装胶束= 0.19) 和约 -69.8 mV 的 zeta 电位。同时，与载药SA聚集体相比，载药RAOA微胶囊具有相对较高的87.6%的包封率（EE）和良好的缓释特性，表明RAOA对疏水性布洛芬具有良好的亲和力。RAOA微胶囊的溶胀降解和负载药物的扩散共同控制了布洛芬的释放速率。此外，它对 RAW264.7 细胞也显示出低细胞毒性，类似于 SA 聚集体。