{"title":"治疗脓毒症诱发的急性肺损伤的辛伐他汀载体纳米脂质体输送系统","authors":"Jianhai Yang, Yue Yue","doi":"10.1166/jbn.2024.3805","DOIUrl":null,"url":null,"abstract":"To enhance the treatment of acute lung injury (ALI) induced by sepsis and optimize the clinical efficacy of simvastatin (SV), we develop SV-loaded nanoliposomes (SV/NLC) as a novel drug delivery system. The NLCs exhibited a particle size of approximately 165 nm, which increased to around\n 195 nm upon SV loading. NLCs significantly prolonged the half-life of SV by nearly five-fold and improved its penetration into EA.hy926 cells, demonstrating excellent biocompatibility and targeted delivery for ALI therapy. In the rat model of ALI, the SV/NLC effectively reduced the lung wet/dry\n ratio and the levels of inflammatory factor and albumin in the alveoli, thus improving the alveolar gas exchange function and blood oxygenation. The SV/NLC group demonstrated superior suppression of oxidative stress within lung tissues compared to other groups. Notably, treatment with SV reduction\n in TLR4, MyD88, and NF-κB P65 levels in lung tissues from ALI rat models. This effect was particularly pronounced in the SV/NLC group. Furthermore, SV can effectively mitigate inflammatory responses and oxidative stress in ALI treatment by modulating the TLR4/NF-κB\n signaling pathway. In conclusion, our findings suggest that SV can exert therapeutic effects against sepsis-induced ALI through inhibition of the TLR4/NF-κ and mitigate inflammatory response and oxidative stress.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Simvastatin-Loaded Nanoliposome Delivery System for Sepsis-Induced Acute Lung Injury\",\"authors\":\"Jianhai Yang, Yue Yue\",\"doi\":\"10.1166/jbn.2024.3805\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"To enhance the treatment of acute lung injury (ALI) induced by sepsis and optimize the clinical efficacy of simvastatin (SV), we develop SV-loaded nanoliposomes (SV/NLC) as a novel drug delivery system. The NLCs exhibited a particle size of approximately 165 nm, which increased to around\\n 195 nm upon SV loading. NLCs significantly prolonged the half-life of SV by nearly five-fold and improved its penetration into EA.hy926 cells, demonstrating excellent biocompatibility and targeted delivery for ALI therapy. In the rat model of ALI, the SV/NLC effectively reduced the lung wet/dry\\n ratio and the levels of inflammatory factor and albumin in the alveoli, thus improving the alveolar gas exchange function and blood oxygenation. The SV/NLC group demonstrated superior suppression of oxidative stress within lung tissues compared to other groups. Notably, treatment with SV reduction\\n in TLR4, MyD88, and NF-κB P65 levels in lung tissues from ALI rat models. This effect was particularly pronounced in the SV/NLC group. Furthermore, SV can effectively mitigate inflammatory responses and oxidative stress in ALI treatment by modulating the TLR4/NF-κB\\n signaling pathway. In conclusion, our findings suggest that SV can exert therapeutic effects against sepsis-induced ALI through inhibition of the TLR4/NF-κ and mitigate inflammatory response and oxidative stress.\",\"PeriodicalId\":15260,\"journal\":{\"name\":\"Journal of biomedical nanotechnology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of biomedical nanotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1166/jbn.2024.3805\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of biomedical nanotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1166/jbn.2024.3805","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
摘要
为了加强对脓毒症诱发的急性肺损伤(ALI)的治疗并优化辛伐他汀(SV)的临床疗效,我们开发了一种新型给药系统--SV负载纳米脂质体(SV/NLC)。纳米脂质体的粒径约为 165 nm,载入 SV 后粒径增至约 195 nm。NLCs 将 SV 的半衰期延长了近五倍,并提高了 SV 在 EA.hy926 细胞中的穿透力,证明了其在 ALI 治疗中出色的生物相容性和靶向递送能力。在大鼠 ALI 模型中,SV/NLC 有效降低了肺干湿比以及肺泡中的炎症因子和白蛋白水平,从而改善了肺泡气体交换功能和血氧饱和度。与其他组相比,SV/NLC 组能更好地抑制肺组织内的氧化应激。值得注意的是,SV 治疗降低了 ALI 大鼠肺组织中 TLR4、MyD88 和 NF-κB P65 的水平。这种效应在 SV/NLC 组中尤为明显。此外,SV 还能通过调节 TLR4/NF-κB 信号通路,有效缓解 ALI 治疗过程中的炎症反应和氧化应激。总之,我们的研究结果表明,SV 可通过抑制 TLR4/NF-κ 发挥治疗脓毒症诱发的 ALI 的作用,并减轻炎症反应和氧化应激。
A Simvastatin-Loaded Nanoliposome Delivery System for Sepsis-Induced Acute Lung Injury
To enhance the treatment of acute lung injury (ALI) induced by sepsis and optimize the clinical efficacy of simvastatin (SV), we develop SV-loaded nanoliposomes (SV/NLC) as a novel drug delivery system. The NLCs exhibited a particle size of approximately 165 nm, which increased to around
195 nm upon SV loading. NLCs significantly prolonged the half-life of SV by nearly five-fold and improved its penetration into EA.hy926 cells, demonstrating excellent biocompatibility and targeted delivery for ALI therapy. In the rat model of ALI, the SV/NLC effectively reduced the lung wet/dry
ratio and the levels of inflammatory factor and albumin in the alveoli, thus improving the alveolar gas exchange function and blood oxygenation. The SV/NLC group demonstrated superior suppression of oxidative stress within lung tissues compared to other groups. Notably, treatment with SV reduction
in TLR4, MyD88, and NF-κB P65 levels in lung tissues from ALI rat models. This effect was particularly pronounced in the SV/NLC group. Furthermore, SV can effectively mitigate inflammatory responses and oxidative stress in ALI treatment by modulating the TLR4/NF-κB
signaling pathway. In conclusion, our findings suggest that SV can exert therapeutic effects against sepsis-induced ALI through inhibition of the TLR4/NF-κ and mitigate inflammatory response and oxidative stress.