Pulmonary endothelium-targeted nanoassembly of indomethacin and superoxide dismutase relieves lung inflammation.
10.1016/j.apsb.2023.05.024
- Author:
Yi YANG
1
;
Makhloufi ZOULIKHA
1
;
Qingqing XIAO
2
;
Feifei HUANG
2
;
Qi JIANG
2
;
Xiaotong LI
2
;
Zhenfeng WU
3
;
Wei HE
1
Author Information
1. Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China.
2. School of Pharmacy, China Pharmaceutical University, Nanjing 2111198, China.
3. Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
- Publication Type:Journal Article
- Keywords:
Acute lung injury;
Codelivery;
Indomethacin;
Inflammation;
Nanocrystals;
Pulmonary endothelium;
Superoxide dismutase
- From:
Acta Pharmaceutica Sinica B
2023;13(11):4607-4620
- CountryChina
- Language:English
-
Abstract:
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.
