School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia; Adelaide Biofilm Test Facility, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
J Pharm Sci. 2017 Dec;106(12):3556-3563. doi: 10.1016/j.xphs.2017.08.006. Epub 2017 Aug 31.
Extracellular polymeric substances in bacterial biofilms reduce the penetration of antimicrobials and give rise to extreme recalcitrance and treatment challenges for many persistent biofilms and associated infections. Nitric oxide (NO) is a promising alternative to conventional antimicrobials but is challenging to deliver at precise concentrations for significant periods in a convenient and nontoxic manner. Here we report a unique NO delivery platform by incorporating the NO precursor isosorbide mononitrate (ISMN) into chitosan gels to facilitate sustained ISMN release and effective delivery. The chitosan gels were characterized with respect to the drug release kinetics, rheological properties, as well as antimicrobial efficacy against biofilms of Staphylococcus aureus in the absence and presence of the antibiotic ciprofloxacin. Chitosan gels loaded with ISMN alone (CS-ISMN) showed comparable antimicrobial effects compared to blank chitosan gel (approximately 2 log reduction). However, there was strong synergy of CS-ISMN when combined with ciprofloxacin, that is, ∼4 log reduction of bacterial colonies of CS-ISMN-CIP compared to the single treatments. These findings were confirmed by confocal imaging and highlight a potentially effective new way to overcome recalcitrant S aureus biofilms using NO precursors.
细菌生物膜中的细胞外聚合物质会降低抗生素的渗透能力，导致许多持久性生物膜和相关感染的耐药性极高，治疗极具挑战性。一氧化氮 (NO) 是一种很有前途的传统抗生素替代品，但以方便且无毒的方式在精确浓度下长时间输送具有挑战性。在这里，我们通过将一氧化氮前体单硝酸异山梨酯 (ISMN) 掺入壳聚糖凝胶中来报告一种独特的 NO 输送平台，以促进 ISMN 的持续释放和有效输送。对壳聚糖凝胶进行了药物释放动力学、流变特性以及在不存在和存在抗生素环丙沙星的情况下对金黄色葡萄球菌生物膜的抗菌功效的表征。单独加载 ISMN 的壳聚糖凝胶 (CS-ISMN) 显示出与空白壳聚糖凝胶相当的抗菌效果（约 2 对数减少）。然而，CS-ISMN 与环丙沙星联合使用时有很强的协同作用，即 CS-ISMN-CIP 的细菌菌落减少了约 4 对数，与单一治疗相比。共聚焦成像证实了这些发现，并强调了使用 NO 前体克服耐药性金黄色葡萄球菌生物膜的一种潜在有效新方法。
