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Pulmonary endothelium-targeted nanoassembly of indomethacin and superoxide dismutase relieves lung inflammation

Yang, Yi ; Zoulikha, Makhloufi ; Xiao, Qingqing ; Huang, Feifei ; Jiang, Qi ; Li, Xiaotong ; Wu, Zhenfeng ; He, Wei

Acta pharmaceutica Sinica. B, 2023-11, Vol.13 (11), p.4607-4620 [Periódico revisado por pares]

Elsevier B.V

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  • Título:
    Pulmonary endothelium-targeted nanoassembly of indomethacin and superoxide dismutase relieves lung inflammation
  • Autor: Yang, Yi ; Zoulikha, Makhloufi ; Xiao, Qingqing ; Huang, Feifei ; Jiang, Qi ; Li, Xiaotong ; Wu, Zhenfeng ; He, Wei
  • Assuntos: Acute lung injury ; Codelivery ; Indomethacin ; Inflammation ; Nanocrystals ; Original ; Pulmonary endothelium ; Superoxide dismutase
  • É parte de: Acta pharmaceutica Sinica. B, 2023-11, Vol.13 (11), p.4607-4620
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    These authors made equal contributions to this work.
  • Descrição: Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction. Herein, we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin (IND) and antioxidant superoxide dismutase (SOD) by assembling the biopharmaceutical SOD onto the “vector” of rod-like pure IND crystals, followed by coating with anti-ICAM-1 antibody (Ab) for targeting endothelial cells. The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39% IND and 2.3% SOD. Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide (LPS)-induced inflammatory murine model. Particularly, the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect. In vitro, the preparation shows the synergistic anti-inflammatory and antioxidant effects in LPS-activated endothelial cells. In vivo, the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers, such as TNF-α, IL-6, COX-2, and reactive oxygen species (ROS), in the lungs. In conclusion, the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation. The study offers a promising approach to combat pulmonary endothelium-associated diseases. The codelivery system Ab-INRplex attaches to the ICAM-1 overexpressed on inflamed endothelial cells, and synergistically relieves the inflammation by inhibiting COX-2 and reactive oxygen species production. [Display omitted]
  • Editor: Elsevier B.V
  • Idioma: Inglês
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