Schiff base-containing dextran nanogel as pH-sensitive drug delivery system of doxorubicin: Synthesis and characterization
Schiff base-containing dextran nanogel as pH-sensitive drug delivery system of doxorubicin: Synthesis and characterization
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含有席夫碱的右旋糖酐纳米凝胶作为阿霉素 pH 敏感药物递送系统：合成和表征
DOI：
10.1177/0885328218783969
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发表时间：
2018-08-01
影响因子：
2.9
通讯作者：
Shan, Shaoyun
中科院分区：
文献类型：
--
作者：
Su, Hongying;Zhang, Wen;Shan, Shaoyun
刺激反应型水凝胶由于具有良好的生物相容性和对外部生理环境因素的响应性，作为载体系统得到了广泛的研究。在本研究中，利用逆微乳液技术，通过席夫碱形成制备了葡聚糖基共价共轭阿霉素（DOX）纳米凝胶。由于希夫碱键是酸敏感的，因此负载dox的纳米凝胶的药物释放谱将依赖于ph值。体外释药研究证实，DOX在酸性条件下（pH 2.0、5.0）的释药速度明显快于pH 7.4。在pH为2.0、5.0和7.4的条件下，72小时内分别释放约66%、28%和9%的药物。人乳腺癌细胞（MCF-7）的细胞摄取表明，负载dox的葡聚糖纳米凝胶可以通过内吞作用被内化，并分布在肿瘤细胞内的内吞区。这些结果表明，含席夫碱的纳米凝胶可以作为ph敏感的药物递送系统。纳米凝胶上存在的多个醛基团可用于靶向配体或成像探针的进一步偶联。
Stimuli-responsive hydrogels have been widely researched as carrier systems, due to their excellent biocompatibility and responsiveness to external physiologic environment factors. In this study, dextran-based nanogel with covalently conjugated doxorubicin (DOX) was developed via Schiff base formation using the inverse microemulsion technique. Since the Schiff base linkages are acid-sensitive, drug release profile of the DOX-loaded nanogel would be pH-dependent. In vitro drug release studies confirmed that DOX was released much faster under acidic condition (pH 2.0, 5.0) than that at pH 7.4. Approximately 66, 28, and 9% of drug was released in 72 h at pH 2.0, 5.0, and 7.4, respectively. Cell uptake by the human breast cancer cell (MCF-7) demonstrated that the DOX-loaded dextran nanogel could be internalized through endocytosis and distributed in endocytic compartments inside tumor cells. These results indicated that the Schiff base-containing nanogel can serve as a pH-sensitive drug delivery system. And the presence of multiple aldehyde groups on the nanogel are available for further conjugations of targeting ligands or imaging probes.