Dexamethasone-loaded ROS-responsive poly(thioketal) nanoparticles suppress inflammation and oxidative stress of acute lung injury

ROS-responsive polymer nanoparticles with enhanced loading of dexamethasone effectively modulate the lung injury microenvironment

“…The cell viability was inhibited by free DEX in RAW264.7 cells, while no obvious inhibition was found by the PFTU NPs and PFTU@DEX NPs ( Fig. 2 B), which is consistent with previous finding that ROS-responsive polymer NPs (PTKNPs) loaded with DEX have no notable toxicity to RAW264.7 cells [41] . These experimental data suggest that the PFTU NPs, as a carrier, might protect cells against drug toxicity and prevent cells from being exposed to excessive drug concentrations.…”

COVID-19 inflammation and implications in drug delivery

“…In order to deliver the anti-COVID-19 agents, either immunomodulator or not, in a selective and specific manner to the injury site, drug delivery systems can be modified to smartly respond to the specific stimuli of the inflammatory microenvironment by releasing their cargo ( Table 2 ) [ [96] , [97] , [98] , [99] ]. The inflammatory biochemical stimulus can be the low pH, the high level of reactive oxygen species (ROS), or the overexpressed inflammatory enzymes [ 95 , 100 ].…”

“… LPS-induce ALI Intravenous [ 97 ] Tempol-phenylboronic acid pinacol- β -cyclodextrin NPs Tempol 109 nm −16 mV Enhanced hydrolysis of PBAP (phenylboronic acid pinacol ester) group in the presence of high concentrations of ROS due to its oxidation-labile units LPS-induce ALI Intravenous [ 99 ] Poly(thioketal) polymeric NPs Dexamethasone 307 nm −22 mV Cleavage of thioketal bonds by the high level of ROS in the injury site. LPS-induce ALI Intravenous [ 98 ] …”

“…Currently, a randomized, double-blind clinical study (NCT04729595) is evaluating its efficiency against COVID-19. Also, Zhai et al [ 98 ] employed PPADT (poly(1,4- phenyleneacetonedimethylene thioketal)) and PTKU (polythioketal urethane) polymers to encapsulate dexamethasone. The high level of ROS in the inflammatory sites could cause the cleavage of thioketal bonds of the polymeric DDS, leading to a local release of their cargo and improved anti-inflammation against LPS-induced ALI.…”

“…The high level of ROS in the inflammatory sites could cause the cleavage of thioketal bonds of the polymeric DDS, leading to a local release of their cargo and improved anti-inflammation against LPS-induced ALI. Besides the enhanced lung accumulation, the decreased ROS level due to their interaction with NPs contributed to the resolution of the injury [ 98 ].…”