Inhalable multi-stimulus sensitive curcumin-alginate nanogels for scavenging reactive oxygen species and anti-inflammatory co-ordination to alleviate acute lung injury.

Acute lung injury (ALI) is one of the most common and extremely critical clinical conditions, which progresses with an inflammatory response and overproduction of reactive oxygen species (ROS), leading to oxidative damage to the lungs. Curcumin (Cur) has great potential in treating ALI due to its excellent antioxidant and anti-inflammatory effects. In this study, Cur and alginate were cross-linked by zinc ions and intermolecular hydrogen bonding to form an inhalable aqueous nanogel system to overcome Cur's low solubility and bioavailability. Cur-alginate (ZA-Cur) nanogels exhibited superior antioxidant properties and down-regulated inflammation-associated factors in vitro with controlled-release behavior under multi-stimulus conditions such as temperature, pH, and ions. Meanwhile, the nanogels system could effectively scavenge cellular ROS to repair oxidative stress damage. In a mice model of ALI, tracheal nebulised inhalation of ZA-Cur nanogels down-regulated the expression of inflammation-related genes such as TNF-α, IL-1β, and IL-6, as well as modulated MDA content and CAT activity to attenuate oxidative stress injury, showing promising lung-protective effects. In conclusion, this work developed inhalable ZA-Cur nanogels to decelerate the progression of lesions in ALI by scavenging intracellular ROS and alleviating inflammation simultaneously, which may be a promising strategy for treating ALI.