Venetoclax nanomedicine alleviates acute lung injury via increasing neutrophil apoptosis. (25th May 2021)

• Record Type: Journal Article
• Authors: Su, Ruonan; Wang, Haixia; Xiao, Chunsheng; Tao, Yu; Li, Mingqiang; Chen, Zhuanggui
• Is Part Of: Biomaterials science. Volume 9:Number 13(2021)
• Page Start: 4746
• Page End: 4754
• Publication Date: 2021-05-25
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d1bm00481f
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : A nano-formulation of the Bcl-2 inhibitor venetoclax was developed to alleviate acute lung injury by increasing neutrophil apoptosis. Abstract : Delayed neutrophil apoptosis has been proved to be closely associated with acute lung injury. A Bcl-2 inhibitor, venetoclax, can improve the clinical outcome of acute lung injury based on its pro-apoptotic effect. However, pulmonary delivery of free venetoclax is hindered by its water insolubility, which results in limited bioavailability and pharmacological effects. An amphipathic polymer-based nanodelivery system has been extensively used to improve the delivery of this insoluble drug and enhance its bioavailability. In this study, an amphiphilic poly(ethylene glycol) modified poly(α-lipoic acid) nanoparticle with an extended lung tissue-resident time was utilized to deliver venetoclax. Compared to free venetoclax, the nanoformulated venetoclax (Nf-venetoclax) presented better efficacy for acute lung injury through increasing neutrophil apoptosis in vivo . In addition, a stronger pro-apoptotic effect of Nf-venetoclax was also demonstrated in vitro . Our study provides encouraging evidence that Nf-venetoclax exhibits effective therapy for acute lung injury.