Triple-layered nanogel for targeted and sustained delivery of florfenicol against bacterial enteritis.

Bacterial enteritis poses a significant challenge to global public health and the livestock industry, necessitating the urgent development of an oral antibacterial formulation with high efficiency, amplified targeting capability, and sustained release. In this study, the triple-layered core-shell nanogel composed of sodium carboxymethyl cellulose, sodium tripolyphosphate, and quaternized chitosan was successfully constructed via a layer-by-layer self-assembly strategy for the targeted delivery and sustained release of florfenicol. The prepared triple-layered core-shell nanogel exhibited uniform spherical morphology with 110.0 ± 2.7 nm and -21.2 ± 2.6 mV, and demonstrated excellent hydrogel stability, pH-responsive release behavior, and optimal biosafety standards. Moreover, the triple-layered core-shell nanogel demonstrated elevated bactericidal potency against Escherichia coli relative to the free drug, and the time-kill assay together with bacterial viability assay results confirmed its concentration-dependent bactericidal effect. Scanning electron microscopy further revealed that the nanogel exerted synergistic antibacterial action by inducing bacterial membrane perturbation. In vivo distribution and therapeutic effect indicated that the nanogel possessed excellent retention capacity in the gastrointestinal tract, achieving satisfactory survival rate and cure rate in infected mice, while effectively limiting the excessive upregulation of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and promoting the recovery of the anti-inflammatory cytokine (IL-10), thereby re-establishing the inflammatory and immunomodulatory balance. Collectively, the triple-layered core-shell nanogel developed in this study provides an efficient and safe nanoplatform for the oral treatment of bacterial enteritis through a triple synergistic mechanism involving targeted delivery, enhanced antibacterial activity and immunomodulation.