Department of Smart Green Technology Engineering, Pukyong National University, Busan 48513, South Korea.
Department of Biomedical Engineering, Pukyong National University, Busan 48513, South Korea.
Carbohydr Polym. 2022 Feb 15;278:118964. doi: 10.1016/j.carbpol.2021.118964. Epub 2021 Dec 2.
In this work, novel injectable and reduction-responsive hydrogels were successfully prepared via inverse electron demand Diels-Alder reaction between alginate-norbornene and a water-soluble PEG based disulfide cross-linker. The reduction-responsive cross-linker was designed to contain a PEG chain within two disulfide linkages, and two terminal tetrazine groups. The resulting hydrogels possessed high swelling ratios, porous morphology, excellent drug loading efficiency (~92%), and suitable mechanical properties. The drug release experiments demonstrated that the hydrogels released more than 90% of the encapsulated doxorubicin (DOX) in the presence of 10 mM glutathione while a minimal DOX release (<25%) was measured in physiological buffer (PBS, pH = 7.4) after 11 d. The cross-linker and hydrogels did not exhibit any apparent cytotoxicity to fibroblast cells. In contrast, DOX-loaded hydrogels induced anti-tumor activity against cancer cells. The injectable and reduction-responsive hydrogels hold great potential as a biomaterial for stimuli responsive drug delivery applications.
在这项工作中，通过海藻酸钠-降冰片烯与基于水溶性 PEG 的二硫键交联剂之间的逆电子需求 Diels-Alder 反应，成功制备了新型可注射和还原响应水凝胶。还原响应性交联剂设计为包含两个二硫键和两个末端四嗪基团的 PEG 链。所得水凝胶具有高溶胀比、多孔形态、优异的药物负载效率（约 92%）和合适的机械性能。药物释放实验表明，在 10 mM 谷胱甘肽存在下，水凝胶释放了超过 90%的包封阿霉素（DOX），而在 11 天后生理缓冲液（PBS，pH = 7.4）中仅测量到最小的 DOX 释放（<25%）。交联剂和水凝胶对成纤维细胞没有表现出任何明显的细胞毒性。相比之下，负载 DOX 的水凝胶对癌细胞表现出抗肿瘤活性。可注射和还原响应水凝胶作为刺激响应药物递送应用的生物材料具有巨大的潜力。
