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PEG Functionalized Stimuli Responsive Self-Healable Injectable Dynamic Imino-boronate G-quadruplex Hydrogel for the Delivery of Doxorubicin
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-01-24 , DOI: 10.1021/acsabm.9b01034
Ankan Biswas 1 , Tapas Ghosh 1 , Pramod K Gavel 1 , Apurba K Das 1
Affiliation  

Dynamic G-quadruplex hydrogel is engineered by using guanosine, 2-formylphenylboronic acid, and 4-Arm PEG-NH2. The gelation conditions are optimized by varying concentrations of the gelators, pH, and different alkali metal ions. The formation of imino-boronate bonds during the gelation process is fully characterized with FT-IR, 1H NMR, and 11B NMR spectroscopy. The secondary supramolecular G-quadruplex structure and the formation of nanofibrillar morphology are well examined using several spectroscopic and microscopic techniques. The mechanical strength of the hydrogel is investigated by rheological experiments. The hydrogel is injectable and self-healable due to the dynamic nature of the imono-boronate bonds. The dynamic bonds provide distinct shear-thinning and thixotropic properties to the resulting hydrogel with almost 90% recovery of its mechanical strength after four cycles. The pH responsive behavior of the hydrogel is achieved by pH sensitive imino-boronate bonds, which are unstable at acidic pH. To investigate the biocompatibility of the hydrogel, a wide range of hydrogel concentrations are examined by in vitro cell culture experiments using the MCF-7 cell line. After a biocompatibility test of the hydrogel, the anticancer drug doxorubicin is incorporated inside the gel to analyze the drug release profile at different pHs. The release rate of the loaded drug is observed faster in lower pH (pH 4.8) than in physiological pH (pH 7.4). Different release rate of the drug from the drug loaded hydrogel in different pHs is driven by the pH sensitive imino-boronate bonds. The release profile of the drug is slow, sustain and steady.

中文翻译:

用于递送多柔比星的 PEG 功能化刺激响应性自愈可注射动态亚氨基硼酸盐 G-四链体水凝胶

动态 G-四链体水凝胶是使用鸟苷、2-甲酰基苯基硼酸和 4-Arm PEG-NH 2设计的。通过改变凝胶剂的浓度、pH 值和不同的碱金属离子来优化凝胶化条件。FT-IR、 1 H NMR 和11充分表征了胶凝过程中亚氨基硼酸酯键的形成B核磁共振波谱。使用几种光谱和显微技术很好地检查了二级超分子 G-四链体结构和纳米纤丝形态的形成。通过流变实验研究水凝胶的机械强度。由于单硼酸键的动态特性,水凝胶是可注射和自愈的。动态键为所得水凝胶提供了明显的剪切稀化和触变性,四次循环后其机械强度恢复了近 90%。水凝胶的 pH 响应行为是通过 pH 敏感的亚氨基硼酸键实现的,该键在酸性 pH 下不稳定。为了研究水凝胶的生物相容性,使用 MCF-7 细胞系通过体外细胞培养实验检查了各种水凝胶浓度。在对水凝胶进行生物相容性测试后,将抗癌药物阿霉素掺入凝胶内,以分析不同 pH 值下的药物释放曲线。在较低的 pH (pH 4.8) 中观察到负载药物的释放速率比在生理 pH (pH 7.4) 中更快。在不同的 pH 值下,载药水凝胶中药物的不同释放速率是由 pH 敏感的亚氨基硼酸盐键驱动的。药物的释放曲线缓慢、持续且稳定。在不同的 pH 值下,载药水凝胶中药物的不同释放速率是由 pH 敏感的亚氨基硼酸盐键驱动的。药物的释放曲线缓慢、持续且稳定。在不同的 pH 值下,载药水凝胶中药物的不同释放速率是由 pH 敏感的亚氨基硼酸盐键驱动的。药物的释放曲线缓慢、持续且稳定。
更新日期:2020-01-24
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