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动态交联可注射生物水凝胶作为细胞外基质模拟物用于抗生素递送和3D细胞培养。

Dynamic crosslinked and injectable biohydrogels as extracellular matrix mimics for the delivery of antibiotics and 3D cell culture.

作者信息

Fan Zhiping, Cheng Ping, Liu Min, Prakash Sangeeta, Han Jun, Ding Zhuang, Zhao Yanna, Wang Zhengping

机构信息

Institute of BioPharmaceutical Research, Liaocheng University Liaocheng 252059 China

Liaocheng High-Tech Biotechnology Co. Ltd Liaocheng 252059 China.

出版信息

RSC Adv. 2020 May 22;10(33):19587-19599. doi: 10.1039/d0ra02218g. eCollection 2020 May 20.

Abstract

Antibiotics are widely used in clinical medicine. As an important member, vancomycin often plays an irreplaceable role in some serious infections but for its use, there is still a lack of suitable carriers and effective formulations. To find a vancomycin carrier with potential for clinical applications, a new class of poly(γ-glutamic acid)/dextran-based injectable hydrogels have been constructed through dynamic covalent hydrazone linkages. Adipic dihydrazide (ADH)-grafted poly(γ-glutamic acid) (PGAADH) and sodium periodate-oxidized dextran (OD) precursors were synthesized; then, the hydrogels were formed by blending PGAADH and OD buffer solutions without any additives under physiological conditions. The newly formed precursor structures, mechanical properties, morphologies, hydrogel degradation profiles, and the interaction between the drug and precursors were investigated with FTIR spectroscopy, H NMR spectroscopy, rheological experiments, compression tests, SEM, and isothermal titration calorimetric (ITC) measurements. The resulting hydrogels exhibited excellent antibacterial ability and ideal variable performances. Moreover, the hydrogels exhibited different drug release kinetics and mechanisms and were applied effectively towards the controlled release of vancomycin. Significantly, benefitting from the reversibly cross-linked systems and the excellent biocompatibility, the hydrogels can work as the ideal material for HeLa cell culture, leading to encapsulated cells with higher viability and capacity that is proliferative. Therefore, the injectable PGAADH/OD hydrogels demonstrated attractive properties for future applications in pharmaceutics and tissue engineering.

摘要

抗生素在临床医学中被广泛使用。作为重要一员,万古霉素在一些严重感染中常常发挥着不可替代的作用,但在其应用方面,仍缺乏合适的载体和有效的制剂。为了找到一种具有临床应用潜力的万古霉素载体,通过动态共价腙键构建了一类新型的基于聚(γ-谷氨酸)/葡聚糖的可注射水凝胶。合成了己二酸二酰肼(ADH)接枝的聚(γ-谷氨酸)(PGAADH)和高碘酸钠氧化的葡聚糖(OD)前体;然后,在生理条件下,将PGAADH和OD缓冲溶液在无任何添加剂的情况下混合形成水凝胶。利用傅里叶变换红外光谱(FTIR)、核磁共振氢谱(H NMR)、流变学实验、压缩试验、扫描电子显微镜(SEM)和等温滴定量热法(ITC)测量研究了新形成的前体结构、力学性能、形态、水凝胶降解曲线以及药物与前体之间的相互作用。所得水凝胶表现出优异的抗菌能力和理想的可变性能。此外,水凝胶表现出不同的药物释放动力学和机制,并有效地应用于万古霉素的控释。值得注意的是,受益于可逆交联体系和优异的生物相容性,水凝胶可作为HeLa细胞培养的理想材料,使包封的细胞具有更高的活力和增殖能力。因此,可注射的PGAADH/OD水凝胶在药物制剂和组织工程的未来应用中显示出诱人的特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1fa/9054094/0724116f8715/d0ra02218g-f8.jpg

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