Vu Trung Thang, Yadav Sonyabapu, Reddy Obireddy Sreekanth, Jo Sung-Han, Joo Soo-Bin, Kim Byeong Kook, Park Eun Ju, Park Sang-Hyug, Lim Kwon Taek
Department of Smart Green Technology Engineering, Pukyong National University, Busan 48513, Republic of Korea.
Department of Display Engineering, Pukyong National University, Busan 48513, Republic of Korea.
Pharmaceuticals (Basel). 2023 Jun 5;16(6):841. doi: 10.3390/ph16060841.
Selective delivery of anticancer drug molecules to the tumor site enhances local drug dosages, which leads to the death of cancer cells while simultaneously minimizing the negative effects of chemotherapy on other tissues, thereby improving the patient's quality of life. To address this need, we developed reduction-responsive chitosan-based injectable hydrogels via the inverse electron demand Diels-Alder reaction between tetrazine groups of disulfide-based cross-linkers and norbornene groups of chitosan derivatives, which were applied to the controlled delivery of doxorubicin (DOX). The swelling ratio, gelation time (90-500 s), mechanical strength (G'~350-850 Pa), network morphology, and drug-loading efficiency (≥92%) of developed hydrogels were investigated. The in vitro release studies of the DOX-loaded hydrogels were performed at pH 7.4 and 5.0 with and without DTT (10 mM). The biocompatibility of pure hydrogel and the in vitro anticancer activity of DOX-loaded hydrogels were demonstrated via MTT assay on HEK-293 and HT-29 cancer cell lines, respectively.
将抗癌药物分子选择性递送至肿瘤部位可提高局部药物剂量，这会导致癌细胞死亡，同时将化疗对其他组织的负面影响降至最低，从而改善患者的生活质量。为满足这一需求，我们通过基于二硫键的交联剂的四嗪基团与壳聚糖衍生物的降冰片烯基团之间的逆电子需求狄尔斯-阿尔德反应，开发了还原响应型壳聚糖基可注射水凝胶，并将其应用于阿霉素（DOX）的控释。研究了所开发水凝胶的溶胀率、凝胶化时间（90 - 500秒）、机械强度（G'~350 - 850帕）、网络形态和载药效率（≥92%）。在有无二硫苏糖醇（10 mM）的情况下，于pH 7.4和5.0条件下对载有DOX的水凝胶进行了体外释放研究。分别通过对人胚肾293细胞系和人结肠癌细胞系HT - 29进行MTT测定，证明了纯凝胶的生物相容性以及载有DOX的水凝胶的体外抗癌活性。
