Co-delivery of azithromycin and ibuprofen by ROS-responsive polymer nanoparticles synergistically attenuates the acute lung injury

炎症 活性氧 布洛芬 体内 脂多糖 细胞凋亡 化学 药理学 抗生素 微生物学 阿奇霉素 医学 免疫学 生物 生物化学 生物技术
作者
Wali Muhammad,Yiru Zhang,Jiaqi Zhu,Jieqi Xie,Shuqin Wang,Ruo Wang,Bing Feng,Jiahang Zhou,Wenyi Chen,Yanping Xu,Qigu Yao,Yingduo Yu,Hongcui Cao,Changyou Gao
出处
期刊:Biomaterials advances 卷期号:154: 213621-213621 被引量:3
标识
DOI:10.1016/j.bioadv.2023.213621
摘要

Bacterial infection causes lung inflammation and recruitment of several inflammatory factors that may result in acute lung injury (ALI). During bacterial infection, reactive oxygen species (ROS) and other signaling pathways are activated, which intensify inflammation and increase ALI-related mortality and morbidity. To improve the ALI therapy outcome, it is imperative clinically to manage bacterial infection and excessive inflammation simultaneously. Herein, a synergistic nanoplatform (AZI+IBF@NPs) constituted of ROS-responsive polymers (PFTU), and antibiotic (azithromycin, AZI) and anti-inflammatory drug (ibuprofen, IBF) was developed to enable an antioxidative effect, eliminate bacteria, and modulate the inflammatory milieu in ALI. The ROS-responsive NPs (PFTU NPs) loaded with dual-drugs (AZI and IBF) scavenged excessive ROS efficiently both in vitro and in vivo. The AZI+IBF@NPs eradicated Pseudomonas aeruginosa (PA) bacterial strain successfully. To imitate the entry of bacterial-derived compounds in body, a lipopolysaccharide (LPS) model was adopted. The administration of AZI+IBF@NPs via the tail veins dramatically reduced the number of neutrophils, significantly reduced cell apoptosis and total protein concentration in vivo. Furthermore, nucleotide oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3) and Interleukin-1 beta (IL-1β) expressions were most effectively inhibited by the AZI+IBF@NPs. These findings present a novel nanoplatform for the effective treatment of ALI.
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