1 Department of Chemical Engineering, Kunming University of Science and Technology, Kunming, China.
2 Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China.
J Biomater Appl. 2018 Aug;33(2):170-181. doi: 10.1177/0885328218783969. Epub 2018 Jun 25.
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.
具有刺激响应性的水凝胶因其出色的生物相容性和对外界生理环境因素的响应性而被广泛研究为载体系统。在这项研究中，通过席夫碱形成，使用反相微乳液技术开发了具有共价连接的阿霉素（DOX）的葡聚糖纳米凝胶。由于席夫碱键对酸敏感，因此负载 DOX 的纳米凝胶的药物释放特性将依赖于 pH 值。体外药物释放研究证实，在酸性条件（pH 2.0、5.0）下，DOX 的释放速度比在 pH 7.4 下快得多。在 pH 2.0、5.0 和 7.4 下，分别在 72 小时内释放了约 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隔室内。这些结果表明，含席夫碱的纳米凝胶可以作为一种 pH 敏感的药物传递系统。并且纳米凝胶上存在多个醛基可用于进一步缀合靶向配体或成像探针。
