In this study, chitosan-based hydrogels were produced by incorporating three drugs with a different solubility into a polymer matrix. The lyophilized chitosan salt was prepared using an innovative and less-expensive synthetic process by the freeze-drying technique. Firstly, the three drugs (caffeine, ascorbic acid, and 5-fluorouracil (5-FU)) were selected as model drugs to test the in vitro release behavior of the hydrogel. The drugs were solubilized in chitosan salt, lyophilized, and cross-linked with benzaldehyde involving the formation of a Schiff base with (–C=N-) linkage to produce a physical hydrogel. Subsequently, the physicochemical properties of N-benzyl chitosan and lyophilized chitosan salt were evaluated by Fourier-transform infrared (FTIR) spectra, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The intrinsic viscosity of the conventional chitosan was determined by the Mark–Houwink–Sakurada equation. Moreover, the kinetics of hydrogel swelling and drug release were studied by the UV-visible method at physiological conditions (pH = 7.4 at 37°C). The results show that lyophilized N-benzyl chitosan had a maximum swelling ratio of 720 ± 2% by immersion in phosphate-buffered saline solutions (PBS) (pH = 7.4 at 37°C). In vitro drug releases were evaluated in PBS, and the obtained results show that the maximum drug release after 24 h was 42% for caffeine, 99% for 5-FU, and 94% for ascorbic acid. Then, to optimize the cumulative release of caffeine, Tween 20 was added and 98% as a release percentage was obtained. The drug-loading results were investigated with the Korsmeyer–Peppas kinetic model and applied to determine the drug release mechanism.

中文翻译：

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与苯甲醛交联的冻干壳聚糖基水凝胶的合成和表征用于控制药物释放

在这项研究中，通过将三种具有不同溶解度的药物掺入聚合物基质中来生产基于壳聚糖的水凝胶。冻干壳聚糖盐是通过冷冻干燥技术使用创新且成本较低的合成工艺制备的。首先，选择三种药物（咖啡因、抗坏血酸和5-氟尿嘧啶（5-FU））作为模型药物来测试水凝胶的体外释放行为。将药物溶解在壳聚糖盐中，冻干，并与苯甲醛交联，包括形成具有 (-C=N-) 键的希夫碱以产生物理水凝胶。随后，通过傅里叶变换红外 (FTIR) 光谱、扫描电子显微镜 (SEM) 和热重分析 (TGA) 评估了 N-苄基壳聚糖和冻干壳聚糖盐的理化性质。常规壳聚糖的特性粘度由 Mark-Houwink-Sakurada 方程确定。此外，在生理条件下（pH = 7.4，37°C），通过紫外-可见方法研究了水凝胶溶胀和药物释放的动力学。结果表明，冻干的 N-苄基壳聚糖通过浸入磷酸盐缓冲盐溶液 (PBS)（pH = 7.4，37°C）的最大溶胀率为 720 ± 2%。在 PBS 中评估体外药物释放，所得结果表明，24 小时后的最大药物释放为咖啡因的 42%、5-FU 的 99% 和抗坏血酸的 94%。然后，为了优化咖啡因的累积释放，添加吐温 20 并获得 98% 的释放百分比。用 Korsmeyer-Peppas 动力学模型研究载药结果，并用于确定药物释放机制。