Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin.

Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin.
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DOI:
10.3390/md19030144
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发表时间:
2021-03-06
期刊:
影响因子:
5.4
通讯作者:
Priddy LB
Priddy LB
中科院分区:
医学2区
文献类型:
--
作者:
Tucker LJ;Grant CS;Gautreaux MA;Amarasekara DL;Fitzkee NC;Janorkar AV;Varadarajan A;Kundu S;Priddy LB

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温敏性壳聚糖水凝胶是一种可再生的生物相容性材料,作为可注射的生物材料在多种疾病的局部给药治疗中有着广泛的应用。为了对抗感染,如金黄色葡萄球菌骨髓炎,局部抗生素递送将允许在感染部位使用更高剂量,而没有与传统抗生素方案相关的风险。磷霉素是一种同类中的小抗生素,被装载到具有不同浓度的β-甘油磷酸盐(β-GP)和磷霉素(FOS)的壳聚糖水凝胶系统中。本研究的目的是阐明低聚果糖与壳聚糖水凝胶之间的相互作用。Kirby Bauer试验显示了对S.金黄色葡萄球菌,在高FOS浓度下效力降低,但仅在低β-GP浓度下效力降低。对于反渗透测定,未观察到FOS浓度的影响。流变学测试表明,增加β-GP浓度增加储能模量,同时降低凝胶化温度。核磁共振显示,通过反应12小时,FOS从水凝胶的液体部分中除去。SEM和FTIR证实凝胶在5天内降解并释放有机磷酸酯。这项工作提供了深入了解磷霉素和壳聚糖水凝胶系统之间的物理化学相互作用,并通知选择生物材料成分,以改善感染治疗。
Thermosensitive chitosan hydrogels—renewable, biocompatible materials—have many applications as injectable biomaterials for localized drug delivery in the treatment of a variety of diseases. To combat infections such as Staphylococcus aureus osteomyelitis, localized antibiotic delivery would allow for higher doses at the site of infection without the risks associated with traditional antibiotic regimens. Fosfomycin, a small antibiotic in its own class, was loaded into a chitosan hydrogel system with varied beta-glycerol phosphate (β-GP) and fosfomycin (FOS) concentrations. The purpose of this study was to elucidate the interactions between FOS and chitosan hydrogel. The Kirby Bauer assay revealed an unexpected concentration-dependent inhibition of S. aureus, with reduced efficacy at the high FOS concentration but only at the low β-GP concentration. No effect of FOS concentration was observed for the planktonic assay. Rheological testing revealed that increasing β-GP concentration increased the storage modulus while decreasing gelation temperature. NMR showed that FOS was removed from the liquid portion of the hydrogel by reaction over 12 h. SEM and FTIR confirmed gels degraded and released organophosphates over 5 days. This work provides insight into the physicochemical interactions between fosfomycin and chitosan hydrogel systems and informs selection of biomaterial components for improving infection treatment.
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