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

Nannan Leng,1,2,* Jinhuan Liu,1,3,* Yongtao Jiang,1 Ning Du,4 Ali Sobhy Dawood,5 Samah Attia Algharib,6 Wanhe Luo1,2 1College of Animal Science and Technology, Tarim University, Alar, Xinjiang, China; 2Key Laboratory of Livestock and Forage Resources Utilization around Tarim, Ministry of Agriculture and Rural Areas, Tarim University, Alar, Xinjiang, China; 3College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China; 4Instrumental Analysis Center, Tarim University, Alar, Xinjiang, China; 5Infectious Diseases Department, Faculty of Veterinary Medicine, University of Sadat City, Sadat city, Egypt; 6Faculty of Veterinary Medicine, Benha University, Moshtohor, Egypt*These authors contributed equally to this workCorrespondence: Wanhe Luo, Email [email protected] Samah Attia Algharib, Email [email protected]: 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