Polypeptide Nanomicrospheres Delivering Dexmedetomidine Mitigate Intestinal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammation.

Abstract

AIMS: This study aims to evaluate the protective effects of dexmedetomidine-loaded polypeptide nanomicrospheres (PNM@Dex) in a mouse model of intestinal ischemia/reperfusion (I/R) injury and investigate the underlying molecular mechanisms, focusing on autophagy activation in enteric neurons. RESULTS: PNM@Dex, synthesizedsolid-phase peptide synthesis and coprecipitation, exhibited uniform spherical morphology (∼150 nm) and high drug encapsulation efficiency.studies demonstrated that PNM@Dex promoted autophagy in enteric neurons, attenuated oxidative stress and apoptosis, and improved cell viability.administration significantly mitigated intestinal injury, suppressed inflammatory cytokine production, and increased the expression of autophagy-related proteins. Autophagy inhibition assays confirmed the essential role of autophagy in mediating the protective effects of PNM@Dex. INNOVATION: This study represents the first successful incorporation of dexmedetomidine into polypeptide nanomicrospheres for targeted delivery to enteric neurons. The nanoplatform achieved sustained release, enhanced autophagy, and exerted strong anti-inflammatory and antioxidant effects, offering a novel therapeutic approach for intestinal I/R injury and potential protection in intestinal transplantation. CONCLUSION: PNM@Dex effectively alleviated intestinal I/R-induced damage through autophagy induction, oxidative stress reduction, and inflammation modulation, underscoring its promise as a therapeutic strategy for intestinal protection and transplantation.44, 213-235.