Self-assembled and intestine-targeting florfenicol nano-micelles effectively inhibit drug-resistant Salmonella typhimurium,eradicate biofilm,and maintain intestinal homeostasis
10.1016/j.jpha.2025.101226
- Author:
Runan ZUO
1
;
Linran FU
1
;
Wanjun PANG
1
;
Lingqing KONG
1
;
Liangyun WENG
1
;
Zeyuan SUN
1
;
Ruichao LI
1
;
Shaoqi QU
1
;
Lin LI
1
Author Information
1. Animal-derived Food Safety Innovation Team,Pharmacology and Toxicology Laboratory,College of Veterinary Medicine,Anhui Agricultural University,Hefei,230036,China
- Publication Type:Journal Article
- Keywords:
Self-assembly;
Intestine targeting nano-micelles;
Florfenicol;
Drug-resistant Salmonella typhimurium;
Biofilm eradication;
Intestinal homeostatic maintenance
- From:
Journal of Pharmaceutical Analysis
2025;15(7):1585-1605
- CountryChina
- Language:English
-
Abstract:
Antimicrobial resistance(AMR)is a growing public health crisis that requires innovative solutions.Emerging multidrug resistant(MDR)Salmonella typhimurium has raised concern for its effect on path-ogenic infection and mortality in humans caused by enteric diseases.To combat these MDR Salmonella typhimurium pathogens,highly effective and broad-spectrum antibiotics such as flufenicol(FFC)need to be evaluated for their potent antibacterial activity against Salmonella typhimurium.However,the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR.In this work,we develop a novel nano-formulation,flufenicol nano-micelles(FTPPM),which are based on D-α-tocopherol polyethylene glycol 1,000 succinate(TPGS)/poloxamer 188(P188),for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine.Herein,FTPPM were prepared via a thin film hydration method.The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems,which can further decrease pro-duction costs.The optimized FTPPM demonstrated outstanding stability and sustained release.An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy(68.17％)than did florfenicol-loaded TPGS polymer micelles(FTPM),flufenicol active pharmaceutical ingredients(FFC-API),and flufenicol commercially available medicine(FFC-CAM),and also exhibited outstanding biocompatibility.Notably,FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms.More importantly,FTPPM effectively restored intestinal flora dis-orders induced by drug-resistant Salmonella typhimurium in mice.In summary,FTPPM significantly improved the solubility and oral bioavailability of florfenicol,enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo.FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.
