College of Pharmacy, Pusan National University, Busan, South Korea.
College of Pharmacy, Pusan National University, Busan, South Korea; Department of Cogno-Mechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan, South Korea.
Eur J Pharm Biopharm. 2018 Nov;132:94-102. doi: 10.1016/j.ejpb.2018.09.009. Epub 2018 Sep 14.
Methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds have become a significant clinical issue worldwide. Recently, nitric oxide (NO) has emerged as a potent antibacterial agent against MRSA infections and a wound-healing enhancer. Nevertheless, clinical applications of NO have been largely restricted by its gaseous state and short half-life. In this study, our aim was to develop S-nitrosoglutathione (GSNO, an endogenous NO donor)-loaded poly(lactic-co-glycolic acid) [PLGA] microparticles (GSNO-MPs) that release NO over a prolonged period, to accelerate the healing of MRSA-infected wounds with less frequent dosing. GSNO was successfully encapsulated into PLGA microparticles by a solid-in-oil-in-water emulsion solvent evaporation method. Scanning electron microscopy and X-ray diffraction analyses confirmed the successful fabrication of GSNO-MPs. The latter released NO in a prolonged manner over 7 days and exerted a remarkable antibacterial activity against MRSA in a concentration- and time-dependent manner. Moreover, GSNO-MPs had good antibacterial efficacy and were found to accelerate wound healing in a mouse model of MRSA-infected wounds. Therefore, NO-releasing MPs devised in this study may be a promising option for the treatment of cutaneous wounds infected by drug-resistant bacteria such as MRSA.
耐甲氧西林金黄色葡萄球菌（MRSA）感染的伤口已成为全球范围内的一个重大临床问题。最近，一氧化氮（NO）作为一种有效的抗 MRSA 感染和促进伤口愈合的抗菌剂而备受关注。然而，NO 的临床应用受到其气体状态和半衰期短的限制。在这项研究中，我们的目的是开发 S-亚硝基谷胱甘肽（GSNO，一种内源性 NO 供体）负载的聚（乳酸-共-乙醇酸）[PLGA] 微球（GSNO-MPs），以实现 NO 的长时间释放，从而减少给药频率，加速 MRSA 感染伤口的愈合。通过油包水乳液溶剂蒸发法成功地将 GSNO 包封到 PLGA 微球中。扫描电子显微镜和 X 射线衍射分析证实了 GSNO-MPs 的成功制备。后者在 7 天内以延长的方式释放 NO，并以浓度和时间依赖的方式对 MRSA 表现出显著的抗菌活性。此外，GSNO-MPs 具有良好的抗菌效果，并在 MRSA 感染伤口的小鼠模型中被发现可加速伤口愈合。因此，本研究中设计的释放 NO 的 MPs 可能是治疗耐甲氧西林金黄色葡萄球菌等耐药菌感染皮肤伤口的一种有前途的选择。
