Qureshi Omer Salman, Zeb Alam, Akram Muhammad, Kim Myung-Sic, Kang Jong-Ho, Kim Hoo-Seong, Majid Arshad, Han Inbo, Chang Sun-Young, Bae Ok-Nam, Kim Jin-Ki
College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi 15588, Republic of Korea.
Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, England, United Kingdom.
Eur J Pharm Biopharm. 2016 Nov;108:187-195. doi: 10.1016/j.ejpb.2016.09.008. Epub 2016 Sep 12.
The aim of this study was to enhance the anti-inflammatory effects of carbon monoxide (CO) via sustained release of CO from carbon monoxide-releasing molecule-2-loaded lipid nanoparticles (CORM-2-NPs). CORM-2-NPs were prepared by hot high pressure homogenization method using trilaurin as a solid lipid core and Tween 20/Span 20/Myrj S40 as surfactant mixture. The physicochemical properties of CORM-2-NPs were characterized and CO release from CORM-2-NPs was assessed by myoglobin assay. In vitro anti-inflammatory effects were evaluated by nitric oxide assay in lipopolysaccharide-stimulated RAW 264.7 macrophages. In vivo anti-inflammatory activity was investigated by measuring paw volumes and histological examination in carrageenan-induced rat paw edema. Spherical CORM-2-NPs were around 100nm with narrow particle size distribution. The sustained CO release from CORM-2-NPs was observed and the half-life of CO release increased up to 10 times compared with CORM-2 solution. CORM-2-NPs showed enhanced in vitro anti-inflammatory effects by inhibition of nitric oxide production. Edema volume in rat paw was significantly reduced after treatment with CORM-2-NPs. Taken together, CORM-2-NPs have a great potential for CO therapeutics against inflammation via sustained release of CO.
本研究的目的是通过负载一氧化碳释放分子-2的脂质纳米颗粒（CORM-2-NPs）持续释放一氧化碳（CO）来增强其抗炎作用。采用热高压均质法，以三月桂精为固体脂质核心，吐温20/司盘20/聚山梨酯40为表面活性剂混合物制备CORM-2-NPs。对CORM-2-NPs的理化性质进行了表征，并通过肌红蛋白测定法评估了CORM-2-NPs中CO的释放情况。通过脂多糖刺激的RAW 264.7巨噬细胞中的一氧化氮测定法评估体外抗炎作用。通过测量角叉菜胶诱导的大鼠足爪水肿中的足爪体积和组织学检查来研究体内抗炎活性。球形CORM-2-NPs直径约为100nm，粒径分布窄。观察到CORM-2-NPs能够持续释放CO，与CORM-2溶液相比，CO释放的半衰期增加了10倍。CORM-2-NPs通过抑制一氧化氮的产生显示出增强的体外抗炎作用。用CORM-2-NPs治疗后，大鼠足爪的水肿体积显著减小。综上所述，CORM-2-NPs通过持续释放CO在炎症的CO治疗方面具有巨大潜力。
