Local delivery of anticancer agents via injectable hydrogels could be a promising method for achieving spatiotemporal control on drug release as well as minimizing the disadvantages related to the systemic mode of drug delivery. Keeping this in mind, we report the development of N,O-carboxymethyl chitosan (N,O-CMCS)–guar gum-based injectable hydrogels for the sustained delivery of anticancer drugs. The hydrogels were synthesized by chemical crosslinking of multialdehyde guar gum (MAGG) and N,O-CMCS through dynamic Schiff base linkages, without requiring any external crosslinker. Fabrication of injectable hydrogels, involving N,O-CMCS and MAGG via Schiff base crosslinking, is being reported for the first time. The hydrogels exhibited pH-responsive swelling behavior and good mechanical properties with a storage modulus of about 1625 Pa. Due to the reversible nature of Schiff base linkages, hydrogels displayed excellent self-healing and thixotropic properties. Doxorubicin (Dox), an anticancer agent, was loaded onto these hydrogels and its release studies were conducted at pH 7.4 (physiological) and pH 5.5 (tumoral). A sustained release of about 67.06% Dox was observed from the hydrogel after 5 days at pH 5.5 and about 32.13% at pH 7.4. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on the human embryonic kidney cell line (HEK-293) and the hemolytic assay demonstrated the biocompatible nature of the hydrogels. The Dox-loaded hydrogel exhibited a significant killing effect against breast cancer cells (MCF-7) with a cytotoxicity of about 72.13%. All the data presented support the efficiency of the synthesized N,O-CMCS/MAGG hydrogel as a biomaterial that may find promising applications in anticancer drug delivery.

中文翻译：

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用于持续抗癌药物输送的可注射、自愈和生物相容性 N,O-羧甲基壳聚糖/多醛瓜尔胶水凝胶

通过可注射水凝胶局部递送抗癌剂可能是实现药物释放的时空控制以及最小化与全身给药方式相关的缺点的一种有前途的方法。牢记这一点，我们报告了N , O -羧甲基壳聚糖 ( N , O -CMCS) - 基于瓜尔胶的可注射水凝胶的开发，用于持续递送抗癌药物。水凝胶是通过多醛瓜尔胶 (MAGG) 和N , O -CMCS 通过动态席夫碱键化学交联合成的，不需要任何外部交联剂。可注射水凝胶的制备，涉及N , O- CMCS 和 MAGG 通过 Schiff 碱交联，首次被报道。水凝胶表现出 pH 响应性溶胀行为和良好的机械性能，储能模量约为 1625 Pa。由于席夫碱键的可逆性质，水凝胶显示出优异的自修复和触变性。阿霉素 (Dox) 是一种抗癌剂，被加载到这些水凝胶上，并在 pH 7.4（生理）和 pH 5.5（肿瘤）下进行释放研究。在 pH 5.5 下 5 天后观察到从水凝胶中持续释放约 67.06% Dox，在 pH 7.4 下持续释放约 32.13%。对人胚胎肾细胞系 (HEK-293) 的 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑测定和溶血测定证明了水凝胶的生物相容性。载有 Dox 的水凝胶对乳腺癌细胞 (MCF-7) 表现出显着的杀伤作用，细胞毒性约为 72.13%。提供的所有数据都支持合成的效率N , O -CMCS/MAGG 水凝胶作为一种生物材料，可能会在抗癌药物递送中找到有前景的应用。