Lee Juho, Kwak Dongmin, Kim Hyunwoo, Kim Jihyun, Hlaing Shwe Phyu, Hasan Nurhasni, Cao Jiafu, Yoo Jin-Wook
College of Pharmacy, Pusan National University, Busan 46241, Korea.
Department of Cogno-Mechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan 46241, Korea.
Pharmaceutics. 2020 Jul 2;12(7):618. doi: 10.3390/pharmaceutics12070618.
-nitrosoglutathione (GSNO) has emerged as a potent agent for the treatment of infected cutaneous wounds. However, fabrication of GSNO-containing nanoparticles has been challenging due to its high hydrophilicity and degradability. The present study aimed to fabricate nanoparticles using newly synthesized GSNO-conjugated poly(lactic--glycolic acid) (PLGA) (GSNO-PLGA; GPNPs). Since hydrophilic GSNO was covalently bound to hydrophobic PLGA, loss of GSNO during the nanoparticle fabrication process was minimized, resulting in sufficient loading efficiency (2.32% of GSNO, 0.07 μmol/mg of NO). Real-time NO release analysis revealed biphasic NO release by GPNPs, including initial burst release within 3 min and continuous controlled release for up to 11.27 h, due to the differential degradation rates of the -SNO groups located at the surface and inside of GPNPs. Since GPNPs could deliver NO more efficiently than GSNO in response to increased interaction with bacteria, the former showed enhanced antibacterial effects against methicillin-resistant (MRSA) at the same equivalent concentrations of NO. Finally, the facilitating effects of GPNPs on infected wound healing were demonstrated in MRSA-challenged full-thickness wound mouse model. Collectively, the results suggested GPNPs as an ideal nanoparticle formulation for the treatment of MRSA-infected cutaneous wounds.
亚硝基谷胱甘肽（GSNO）已成为治疗感染性皮肤伤口的一种有效药物。然而，由于其高亲水性和可降解性，制备含GSNO的纳米颗粒一直具有挑战性。本研究旨在使用新合成的GSNO共轭聚乳酸-乙醇酸共聚物（PLGA）（GSNO-PLGA；GPNPs）制备纳米颗粒。由于亲水性的GSNO与疏水性的PLGA共价结合，纳米颗粒制备过程中GSNO的损失最小化，从而获得了足够的负载效率（GSNO为2.32%，NO为0.07μmol/mg）。实时NO释放分析显示，GPNPs呈现双相NO释放，包括3分钟内的初始突发释放和长达11.27小时的持续控释，这是由于位于GPNPs表面和内部的-SNO基团降解速率不同所致。由于GPNPs与细菌的相互作用增加，其释放NO的效率高于GSNO，因此在相同等效浓度的NO下，前者对耐甲氧西林金黄色葡萄球菌（MRSA）显示出增强的抗菌作用。最后，在MRSA感染的全层伤口小鼠模型中证明了GPNPs对感染伤口愈合的促进作用。总的来说，结果表明GPNPs是治疗MRSA感染性皮肤伤口的理想纳米颗粒制剂。
