Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China.
Department of Orthopedics, Changzhou Municipal Hospital of Traditional Chinese Medicine, Changzhou 213003, China.
Int J Biol Macromol. 2023 Jan 1;224:1294-1302. doi: 10.1016/j.ijbiomac.2022.10.215. Epub 2022 Oct 25.
A simple and smart drug controlled delivery system is developed in this work. Biodegradable mesoporous silica nanoparticles (BMSN) were first synthesized by introducing disulfide during the synthesis of mesoporous silica nanoparticles (MSN), which were used for the loading of methotrexate (MTX), an anti-cancer drug. The MTX loaded BMSN (BMSN-MTX) was then encapsulated in the hydrogels of carboxymethyl chitosan (CMCS)/oxidized pullulan (OPL) generated through Schiff base reaction. The acylhydrazone bonds (-N=CH-) between CMCS and OPL are prone to be hydrolyzed in acidic medium while the disulfide linkage (-S-S-) in the BMSN can be cleaved in the presence of glutathione (GSH), and thus the delivery of MTX from the BMSN-MTX-gel can be triggered by both pH and GSH. The results of release kinetics reveal that the delivery of MTX from the biodegradable hydrogels is controlled by Higuchi model. Finally, good biocompatibility and pronounced cytotoxicity of the developed BMSN-MTX-gel are confirmed by cytotoxicity test.
本工作开发了一种简单智能的药物控释体系。通过在介孔硅纳米粒子（MSN）的合成过程中引入二硫键，首次合成了可生物降解的介孔硅纳米粒子（BMSN），并用其负载甲氨蝶呤（MTX），一种抗癌药物。然后，将负载 MTX 的 BMSN（BMSN-MTX）包封在通过席夫碱反应生成的羧甲基壳聚糖（CMCS）/氧化普鲁兰（OPL）水凝胶中。CMCS 和 OPL 之间的酰腙键（-N=CH-）在酸性介质中容易水解，而 BMSN 中的二硫键（-S-S-）在谷胱甘肽（GSH）存在下可以断裂，因此 MTX 可以从 BMSN-MTX-凝胶中通过 pH 和 GSH 触发释放。释放动力学的结果表明，MTX 从可生物降解水凝胶中的释放由 Higuchi 模型控制。最后，通过细胞毒性试验证实了所开发的 BMSN-MTX-凝胶具有良好的生物相容性和显著的细胞毒性。
