Posttraumatic neuroinflammation is a key driver of secondary injury after traumatic brain injury (TBI). Pyroptosis, a proinflammatory form of programmed cell death, considerably activates strong neuroinflammation and amplifies the inflammatory response by releasing inflammatory contents. Therefore, treatments targeting pyroptosis may have beneficial effects on the treatment of secondary brain damage after TBI. Here, a cysteine-alanine-glutamine-lysine peptide–modified β-lactoglobulin (β-LG) nanoparticle was constructed to deliver disulfiram (DSF), C-β-LG/DSF, to inhibit pyroptosis and decrease neuroinflammation, thereby preventing TBI-induced secondary injury. In the post-TBI mice model, C-β-LG/DSF selectively targets the injured brain, increases DSF accumulation, and extends the time of the systemic circulation of DSF. C-β-LG/DSF can alleviate brain edema and inflammatory response, inhibit secondary brain injury, promote learning, and improve memory recovery in mice after trauma. Therefore, this study likely provided a potential approach for reducing the secondary spread of TBI.

Faster recovery and fewer scars are ideal wound healing. We have demonstrated that the cannabinoid receptor 2 (CB₂) agonist Gp1a is beneficial to skin wound healing, which inhibits inflammation and fibrogenesis while promoting re-epithelialization. However, the systemic administration is imprecise and overqualified for a local skin wound. Herein, we prepared Gp1a-gel using triglycerol monostearate (Tm) hydrogel and detected whether the Gp1a-gel worked effectively on mouse skin excision wounds. The results showed that Gp1a-gel might sustainably increase the CB₂ for at least 8 days. It decreased inflammation and fibrogenesis while promoting wound enclosure and re-epithelialization. These results suggested Gp1a-gel may utilize as a potential formulation strategy to treat the skin wound.