Department of Organic Materials Engineering, Chungnam National University, Daejeon 34134, South Korea.
Department of Organic Materials Engineering, Chungnam National University, Daejeon 34134, South Korea.
Int J Biol Macromol. 2023 Jun 15;240:124346. doi: 10.1016/j.ijbiomac.2023.124346. Epub 2023 Apr 6.
Malignant tumors have emerged as a serious health issue, and the interest in developing pH-sensitive polymers for site-specific drug delivery has increased. The physical and/or chemical properties of pH-sensitive polymers depend on the pH, and thus, drugs can be released by cleaving dynamic covalent and/or noncovalent bonds. In this study, gallic acid (GA) was conjugated to chitosan (CS) to prepare self-crosslinked hydrogel beads containing Schiff base (imine bond) crosslinks. The CS-GA hydrogel beads were formed by the dropwise addition of the CS-GA conjugate solution into a Tris-HCl buffer solution (TBS, pH 8.5). The pH-sensitivity of pristine CS was significantly enhanced following the introduction of GA moiety, and as a result, the CS-GA hydrogel beads swelled more than approximately 5000 % at pH 4.0, indicating an excellent swelling/deswelling ability of the beads at different pH (pH 4.0 and 8.5). The reversible breakage/recovery of the imine crosslinks in the CS-GA hydrogel beads was confirmed through X-ray photoelectron spectroscopic and rheological studies. Finally, Rhodamine B was loaded onto the hydrogel beads as a model drug to investigate the pH-sensitive drug release behavior. At pH 4, the drug was released up to approximately 83 % within 12 h. The findings indicate that the CS-GA hydrogel beads have great potential as a drug delivery system that is sensitive to acidic tumor sites in the body.
恶性肿瘤已成为严重的健康问题，因此人们对开发用于靶向药物递送的 pH 敏感聚合物的兴趣日益增加。pH 敏感聚合物的物理和/或化学性质取决于 pH 值，因此可以通过动态共价键和/或非共价键的断裂来释放药物。在这项研究中，将没食子酸（GA）接枝到壳聚糖（CS）上，制备了含有席夫碱（亚胺键）交联的自交联水凝胶珠。通过将 CS-GA 缀合物溶液滴加到 Tris-HCl 缓冲溶液（TBS，pH 8.5）中来形成 CS-GA 水凝胶珠。在引入 GA 部分后，CS 的 pH 敏感性显著增强，并且 CS-GA 水凝胶珠在 pH 4.0 下溶胀超过约 5000%，表明珠子在不同 pH（pH 4.0 和 8.5）下具有出色的溶胀/收缩能力。通过 X 射线光电子能谱和流变学研究证实了 CS-GA 水凝胶珠中亚胺交联的可逆断裂/恢复。最后，将罗丹明 B 负载到水凝胶珠上作为模型药物，以研究 pH 敏感的药物释放行为。在 pH 4 下，药物在 12 小时内释放了约 83%。研究结果表明，CS-GA 水凝胶珠具有作为药物递送系统的巨大潜力，该系统对体内酸性肿瘤部位敏感。
