Intratracheal delivery of macrophage targeted Celastrol-loaded PLGA nanoparticles for enhanced anti-inflammatory efficacy in acute lung injury mice.

Autor: Yao Y; The First Dongguan Affiliated Hospital, Research Center of Nano Technology and Application Engineering, Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China; School of Pharmacology, Guangdong Medical University, Dongguan 523808, China., Fan S; The First Dongguan Affiliated Hospital, Research Center of Nano Technology and Application Engineering, Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China; School of Pharmacology, Guangdong Medical University, Dongguan 523808, China., Fan Y; The First Dongguan Affiliated Hospital, Research Center of Nano Technology and Application Engineering, Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China., Shen X; The First Dongguan Affiliated Hospital, Research Center of Nano Technology and Application Engineering, Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China; School of Pharmacology, Guangdong Medical University, Dongguan 523808, China., Chai X; Laboratory Animal Center, School of Medical Technology, Guangdong Medical University, Dongguan 523808, China., Pi J; Laboratory Animal Center, School of Medical Technology, Guangdong Medical University, Dongguan 523808, China., Huang X; Laboratory Animal Center, School of Medical Technology, Guangdong Medical University, Dongguan 523808, China., Shao Y; The First Dongguan Affiliated Hospital, Research Center of Nano Technology and Application Engineering, Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China., Zhou Z; The First Dongguan Affiliated Hospital, Research Center of Nano Technology and Application Engineering, Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China; School of Pharmacology, Guangdong Medical University, Dongguan 523808, China. Electronic address: zhikunzhou@126.com., Zhao Y; The First Dongguan Affiliated Hospital, Research Center of Nano Technology and Application Engineering, Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China; School of Pharmacology, Guangdong Medical University, Dongguan 523808, China. Electronic address: yuezhao0520@163.com., Jin H; The First Dongguan Affiliated Hospital, Research Center of Nano Technology and Application Engineering, Dongguan Innovation Institute, Guangdong Medical University, Dongguan 523808, China; School of Pharmacology, Guangdong Medical University, Dongguan 523808, China. Electronic address: jinhua0413@gdmu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2024 Nov; Vol. 204, pp. 114511. Date of Electronic Publication: 2024 Sep 21.
DOI: 10.1016/j.ejpb.2024.114511
Abstrakt: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of respiratory failure in critically ill patients. There is still a lack of definitive and effective treatment options, and the mortality rate remains as high as 30% to 40%. Effective therapeutics for ALI/ARDS are greatly hindered by the side effects resulting from inefficient delivery to the disease lesions and off-targeting biodistribution of drugs. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in inflammation processes. Thus, nanodrug to accurately target macrophages have the potential to transform disease treatment. Here, we developed an mannosylated drug delivery system to target and deliver celastrol (Cel) to the alveolar macrophages for enhanced alleviating the cytokines in LPS-induce ALI mice. In vitro data demonstrated that the as-synthesized Man@Cel-NPs significantly improved the targeting of Cel into the inflammatory macrophages via mannose receptor-mediated phagocytosis. In vivo experiments further showed that intratracheal delivery of Man@Cel-NPs can improve the dysregulation of inflammatory response in LPS-induced mice by inhibiting the release of inflammatory cytokines and increasing autophagy and decreasing apoptosis in lungs. This work provides a potential NP platform for the locally tracheal delivery of herbal ingredients and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including ALI/ARDS.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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