Abstract

Medical catheters are essential for clinical diagnosis and therapy, yet their insertion and retention inevitably cause mucosal damage and pain. Conventional catheters compromise comfort and risk secondary inflammation, underscoring the need for advanced catheter surface coatings. Herein, we developed a sprayable lipid-based lubricated hydrogel coating (Oxy@Lipo/Gel) by integrating oxybuprocaine-loaded liposomes (Oxy@Lipo) with an oxidized hyaluronic acid/carboxymethyl chitosan (OHA/CMCS) hydrogel. The OHA/CMCS hydrogel enables rapid spray-induced gelation, while Oxy@Lipo acts as a carrier for the local anesthetic oxybuprocaine. Oxy@Lipo/Gel not only enhances catheter hydrophilicity, reduces interfacial friction and nonspecific protein adsorption, but also exhibits pH-responsive drug release, self-healing capacity, and appropriate degradability. It is worth noting that Lipo dramatically augments the hydrogel's lubricity by reconstruction of phospholipid lubricating interface upon friction-induced migration and surface exposure of Lipo. Furthermore, Oxy@Lipo/Gel-coated endotracheal tube significantly minimize intubation-induced heart rate fluctuations of rhesus monkey, alleviate airway mucosal injury and pain responses effectively, and preserve post-extubation feeding willingness. Mechanistically, Oxy@Lipo/Gel mitigates mucosal damage and pain by activating the Nrf2 pathway for antioxidant defense, inhibiting the pro-inflammatory MAPK cascade, and facilitating M2 macrophage polarization. Collectively, Oxy@Lipo/Gel emerges as a promising strategy to mitigate catheter-related mucosal damage and pain, holding substantial potential for clinical translation and application.