基于接枝二羟咖啡酸壳聚糖和氧化普鲁兰的 pH 响应型黏膜黏附性可注射水凝胶用于局部药物递送。
pH-responsive injectable hydrogels with mucosal adhesiveness based on chitosan-grafted-dihydrocaffeic acid and oxidized pullulan for localized drug delivery.
机构信息
Frontier Institute of Science and Technology, and State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
J Colloid Interface Sci. 2019 Feb 15;536:224-234. doi: 10.1016/j.jcis.2018.10.056. Epub 2018 Oct 20.
Injectable hydrogels with multifunctional properties, including tissue adhesiveness and pH-sensitivity are highly desired for localized drug delivery in disease treatment, and their design is still challenging. We developed a series of multifunctional injectable mucoadhesive and pH-responsive hydrogels based on chitosan-grafted-dihydrocaffeic acid (CS-DA) and oxidized pullulan (OP) via a Schiff base reaction. These hydrogels exhibited good injectability, suitable gelation time, in vitro pH-dependent equilibrated swelling ratios, morphologies, and rheological characteristics. The desirable in vitro pH-sensitive drug release behavior of these hydrogels was demonstrated by a drug release test with anti-cancer drug doxorubicin (DOX) loaded hydrogels at different pH values. The hydrogels showed good DOX release, effectively killing colon tumor cells (HCT116 cells) and good antibacterial properties against E. coli and S. aureus in vitro when the antibacterial model drug amoxicillin was encapsulated in the hydrogels. A lap-shear test was also carried out with these hydrogels. The hydrogels exhibited good mucosal adhesion, indicating their potential use in mucosa-localized drug delivery systems. All these results suggest that these injectable pH-responsive adhesive hydrogels are ideal candidates for development of colon cancer drug delivery carriers or mucoadhesive drug delivery systems.
具有多功能特性的可注射水凝胶，包括组织粘附性和 pH 敏感性，非常适合用于疾病治疗中的局部药物输送，但其设计仍然具有挑战性。我们通过席夫碱反应开发了一系列基于接枝二咖啡酸壳聚糖（CS-DA）和氧化普鲁兰（OP）的多功能可注射型粘弹性和 pH 响应水凝胶。这些水凝胶具有良好的可注射性、合适的凝胶时间、体外 pH 依赖性平衡溶胀比、形态和流变特性。通过载有抗癌药物阿霉素（DOX）的水凝胶在不同 pH 值下的药物释放试验，证明了这些水凝胶具有良好的体外 pH 敏感性药物释放行为。当将抗菌模型药物阿莫西林封装在水凝胶中时，水凝胶表现出良好的 DOX 释放效果，能够有效杀死结肠肿瘤细胞（HCT116 细胞），并具有良好的体外抗菌性能，能够抵抗大肠杆菌和金黄色葡萄球菌。还对这些水凝胶进行了搭接剪切试验。水凝胶表现出良好的粘膜粘附性，表明它们有可能用于粘膜定位药物输送系统。所有这些结果表明，这些可注射的 pH 响应性粘合水凝胶是开发结肠癌药物输送载体或粘膜粘合药物输送系统的理想候选物。
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