Curcumin Loaded ZIF 8 Nanomaterials Ameliorate Porcine Endometritis Like Lesions in a Mouse Model via Regulating Macrophage Polarization and Antibacterial Activity.

Porcine endometritis, primarily resulting from mixed bacterial infections, adversely impacts sow reproductive performance and leads to substantial economic losses in the pig farming sector. Traditional antibiotic treatment is limited due to bacterial resistance and drug residue issues. Curcumin (Cur) possesses inherent antibacterial and anti-inflammatory properties; however, its use is restricted due to limited water solubility and low bioavailability. In this work, dominant pathogens were isolated and identified from vaginal swabs collected from 48 sows with clinical endometritis via 16S rRNA sequencing, followed by antibiotic susceptibility assessment. Cur-loaded ZIF-8 nanoparticles (Cur@ZIF-8) were synthesized for non-antibiotic therapeutic exploration against porcine endometritis. Physicochemical characterizations revealed that Cur@ZIF-8 possessed a hydrodynamic particle size of 106.2 nm, a curcumin loading efficiency of 10.8%, and an encapsulation efficiency of 86.4%. The nanoparticles exhibited uniform morphology, favorable dispersibility, and showed a moderate increase in curcumin release under acidic conditions. Hemolysis assays and mouse toxicity tests confirmed the favorable biocompatibility of Cur@ZIF-8 without obvious toxic effects. In vitro antibacterial evaluations demonstrated that Cur@ZIF-8 exerted potent bactericidal effects, with the minimum inhibitory concentration (MIC) against Proteus mirabilis determined to be 12.5 μg/mL. Consistent with clinical findings, Proteus mirabilis, Staphylococcus aureus, and Escherichia coli were confirmed as the major causative agents of porcine endometritis, which frequently occurred as mixed infections, and these clinical isolates exhibited prominent multi-drug resistance to common antibiotics. Using the isolated dominant clinical strains, we established mouse endometritis models and performed in vivo therapeutic evaluations via uterine bacterial load enumeration, histopathological observation, and immunofluorescence detection of macrophage polarization. The results demonstrated that Cur@ZIF-8 markedly mitigated uterine pathological injury, reduced intrauterine bacterial burden, and alleviated inflammatory infiltration. A decreased semi-quantitative histopathological inflammation score was observed in uterine tissues after Cur@ZIF-8 intervention. Mechanistically, Cur@ZIF-8 remodels the uterine inflammatory microenvironment through the modulation of macrophage polarization, achieving combined antibacterial and anti-inflammatory functions. Collectively, in vivo experiments in mouse endometritis models verified that the Cur@ZIF-8 nanoplatform produces antibacterial and anti-inflammatory effects and exhibits excellent biosafety and biocompatibility. This preclinical study offers a promising non-antibiotic nanotherapeutic candidate and provides an alternative strategy to reduce antibiotic consumption and combat antimicrobial resistance in livestock production; nevertheless, further systematic validation in sow models is still needed to support its practical clinical application for porcine endometritis control.