An esculin-loaded sustained-release hydrogel based on carboxymethyl chitosan and carboxymethyl cellulose for the treatment of endometritis

Endometritis poses a significant economic burden on the livestock industry due to persistent inflammation and impaired reproductive performance. In this study, an injectable esculin-loaded hydrogel (CCE) was developed based on carboxymethyl chitosan and carboxymethyl cellulose sodium crosslinked with genipin to improve the solubility and retention of esculin. The physicochemical properties of the hydrogel, including morphology, particle size, swelling behavior, drug release profile, hemocompatibility, and cytotoxicity, were systematically characterized. The CCE hydrogel exhibited a nanoscale particle size (8.72 nm), high swelling ratio (231%), and sustained drug release behavior (76.5% over 48 h), along with excellent biocompatibility (hemolysis rate < 2.63%). In vitro studies demonstrated that CCE significantly reduced IL-6 and TNF-α secretion in LPS-stimulated bovine endometrial epithelial cells by 52% and 48%, respectively, via inhibition of the TLR4/NF-κB signaling pathway. In vivo, CCE treatment effectively decreased uterine pro-inflammatory cytokine levels, alleviated histopathological damage, and reduced myeloperoxidase activity compared with the LPS group, showing superior therapeutic efficacy over free esculin. This natural polymer-based hydrogel presents a promising platform for localized drug delivery, with strong potential for clinical translation in the treatment of endometritis. Future studies focusing on large-animal models and long-term safety evaluation will further facilitate its clinical application.