Li Caixia, Li Hanxue, Guo Jiahao, Li Liang, Xi Xiaowei, Yu Yanyan
Shanghai General Hospital of Nanjing Medical University 100 Haining Road, Hongkou District Shanghai 200080 P.R. China
Department of Obstetrics and Gynecology, Kunshan Traditional Chinese Medicine Hospital 189 West Chaoyang Road Jiangsu 215300 P.R. China.
RSC Adv. 2020 Jan 2;10(2):689-697. doi: 10.1039/c9ra08986a.
A series of injectable and biocompatible delivery DOX-loaded supramolecular hydrogels were fabricated by using presynthesized DOX-2N-β-CD, Pluronic F-127 and α-CD through host-guest interactions and cooperative multivalent hydrogen bonding interactions. The compositions and morphologies of these hydrogels were confirmed by PXRD and SEM measurements. Moreover, the Rheological measurements of these hydrogels were studied and the studies found that they showed a unique thixotropic behavior, indicting a fast self-healing property after the continuous oscillatory shear stress. Using α-CD as a capping agent, slow and sustained DOX release was observed at different pH values after 72 h. The amount of DOX released at pH 7.4 was determined to be 49.0% for hydrogel 1, whereas the releasing amount of the DOX was increased to 66.3% for hydrogel 1 during the same period at pH 5.5 ( < 0.05), indicating a higher release rate of the drug under more acidic conditions. Taking hydrogel 1 as a representative material, the toxicities of DOX and hydrogel 1 on ovarian cancer cells (SKOV-3) at different exposure durations were examined. The results revealed that hydrogel 1 was less cytotoxic than free DOX to SKOV-3 cells ( < 0.05), suggesting sustained release by these hydrogels in the presence of ovarian cancer cells. It is anticipated that this exploration can provide a new strategy for preparing drug delivery systems.
通过主客体相互作用和多价氢键协同作用,利用预合成的阿霉素 - 2N-β-环糊精(DOX-2N-β-CD)、泊洛沙姆F-127和α-环糊精(α-CD)制备了一系列可注射且具有生物相容性的载阿霉素超分子水凝胶。通过粉末X射线衍射(PXRD)和扫描电子显微镜(SEM)测量确定了这些水凝胶的组成和形态。此外,对这些水凝胶进行了流变学测量,研究发现它们表现出独特的触变性,表明在连续振荡剪切应力后具有快速自愈性能。使用α-环糊精作为封端剂,72小时后在不同pH值下观察到阿霉素的缓慢持续释放。水凝胶1在pH 7.4时阿霉素释放量为49.0%,而在pH 5.5时,同一时期水凝胶1中阿霉素的释放量增加到66.3%(P<0.05),表明在酸性更强的条件下药物释放速率更高。以水凝胶1作为代表性材料,检测了阿霉素和水凝胶1在不同暴露时间对卵巢癌细胞(SKOV-3)的毒性。结果显示,水凝胶1对SKOV-3细胞的细胞毒性低于游离阿霉素(P<0.05),表明这些水凝胶在存在卵巢癌细胞的情况下能持续释放药物。预计这一探索可为制备药物递送系统提供新策略。