Yu Linna, Kong Lingping, Xie Junpeng, Wang Wei, Chang Chen, Che Hongli, Liu Mingzhe
Key Laboratory of Structure-Based Drugs Design & Discovery (Shenyang Pharmaceutical University) of Ministry of Education, Shenyang, P. R. China.
Department of Organic Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, P. R. China.
Des Monomers Polym. 2021 Apr 18;24(1):98-105. doi: 10.1080/15685551.2021.1914398.
Novel monomer, -bis(acryloyl) cystinamide (NBACA), was designed and synthesized with L-cystine as row material. By using this NBACA both as the monomer and crosslinker, reduction-sensitive nanohydrogel was prepared in ethanol via distillation-precipitation polymerization. The obtained nanohydrogel can provide a relatively hydrophobic environment and hydrogen-bonding sites inside the gel; therefore, it is suitable for loading hydrophobic drug. When paclitaxel that possess poor water-solubility was used as a model drug, the nanohydrogel represented a high drug-loading capacity, and dispersed well in aqueous solutions. Furthermore, the disulfide-group-containing nanohydrogel exhibited good reduction-sensitive drug-release behavior. The nanohydrogel biodegraded rapidly in a reducing environment, and released approximately 80% of the PTX within 24 h. Cytotoxicity assays showed that the PTX-loaded nanohydrogel exhibited high cytotoxicity against MCF-7 breast cancer cells, while blank nanohydrogels displayed a negligible cytotoxicity.
以L-胱氨酸为原料设计合成了新型单体双(丙烯酰基)胱氨酸酰胺(NBACA)。以该NBACA为单体和交联剂,通过蒸馏沉淀聚合法在乙醇中制备了还原敏感型纳米水凝胶。所得纳米水凝胶在凝胶内部可提供相对疏水的环境和氢键位点;因此,它适合负载疏水药物。当使用水溶性差的紫杉醇作为模型药物时,纳米水凝胶表现出高载药能力,并且在水溶液中分散良好。此外,含二硫键的纳米水凝胶表现出良好的还原敏感型药物释放行为。纳米水凝胶在还原环境中迅速降解,并在24小时内释放出约80%的紫杉醇。细胞毒性试验表明,负载紫杉醇的纳米水凝胶对MCF-7乳腺癌细胞表现出高细胞毒性,而空白纳米水凝胶的细胞毒性可忽略不计。