Enhanced Antibacterial Effect of pH/Gelatinase-Responsive Florfenicol Nanogels Against Staphylococcus aureus

Abstract

Objective: Staphylococcus aureus ( S. aureus ) commonly endures in the body as small colony variations (SCVs), avoiding the bactericidal effects of drugs and leading to persistent and recurring mastitis infections in cows. Nevertheless, florfenicol is widely dispersed throughout the body and is challenging to penetrate to the targeted site at an appropriate therapeutic dosage, florfenicol’s effectiveness in treating dairy cow mastitis caused by SCVs is comparatively low. Methods: Florfenicol composite nanogels with sustained and targeted release effects were prepared by complexation of β-cyclodextrins (β-CD) and electrostatic interaction between gelatin (positive charge) and γ-polyglutamic acid (γ-PGA) (negative charge) using sodium tripolyphosphate (TPP) (ionic crosslinkers). The optimal formula of florfenicol composite nanogels was screened, and physicochemical characterization, in vitro release, and antibacterial activity of florfenicol composite nanogels were fully evaluated in this work. Results: The optimal formulation was verified by producing florfenicol composite nanogels with 75 mg/mL β-CD, 150 mg/mL gelatin, 10 mg/mL γ-PGA, and 0.5 mg/mL TPP, respectively. The results of physicochemical characterization demonstrated that florfenicol composite nanogels were effectively generated by inclusion and electrostatic interaction. Furthermore, florfenicol composite nanogels exhibited obvious pH/gelatinase-double responsiveness. Furthermore, florfenicol composite nanogels were demonstrated a more potent bacteriostatic and bactericidal action against S. aureus and SCVs. Conclusion: pH/gelatinase-double responsive florfenicol composite nanogels with sustained and targeted release effects can boost the antibacterial activity of florfenicol against SCVs. Keywords: florfenicol, composite nanogels, small colony variants, sustained and targeted release, pH/gelatinase-double responsiveness