H 2 S responsive PEGylated poly (lipoic acid) with ciprofloxacin for targeted therapy of Salmonella.

Autor: Han L; Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China., Liu XW; Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China., Zang T; Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China., Ren H; Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, PR China., Liang DS; Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China., Bai SC; Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China., Li C; Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China., Liao XP; Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, PR China., Liu YH; Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, PR China., Zhang C; Key Laboratory for Biobased Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou 510642, PR China. Electronic address: zhangcq@scau.edu.cn., Sun J; Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, PR China. Electronic address: jiansun@scau.edu.cn.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2022 Nov; Vol. 351, pp. 896-906. Date of Electronic Publication: 2022 Oct 11.
DOI: 10.1016/j.jconrel.2022.09.060
Abstrakt: Targeted antibiotic delivery system would be an ideal solution for the treatment of enteropathogenic infections since it avoids the excessive usage of antibiotics clinically, which may lead to threat on public health and food safety. Salmonella spp. are Enteropathogens, but they are also robust H 2 S producers in the intestinal tracts of hosts. To this end, the PEGylated poly (α lipoic acid) (PEG-PALA) copolymer nanoparticles with hydrophilic exterior and hydrophobic interior were designated in this study to encapsulate the antibiotics and release them in response to H 2 S produced by Salmonella spp. The PEG-PALA nanoparticles demonstrated excellent stability in vitro and biocompatibility toward mammalian Caco-2 and 293 T cells. The release of ciprofloxacin from PEG-PALA nanoparticle was only 25.44 ± 0.57% and 26.98 ± 1.93% (w/w) in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions without H 2 S stimulation. However, the release amounts of ciprofloxacin were up to 73.68 ± 1.63% (w/w) in the presence of 1 mM Na 2 S as H 2 S source. In the mouse infection model, PEG-PALA nanoparticles encapsulated with ciprofloxacin (PEG-PALA@CIP) reduced the Salmonella colonization in the heart, liver, spleen, lung, cecum, and faeces, prolonged ciprofloxacin persistence in the intestine while reducing its absorption into the blood. More importantly, these nanoparticles reduced 3.4-fold of Enterobacteriaceae levels and increased 1.5-fold of the Lactobacillaceae levels compared with the drug administered in the free form. Moreover, these nanoparticles resulted in only minimal signs of intestinal tract inflammation. The H 2 S-responsive antibiotic delivery systems reported in this study demonstrating a variety of advantages including protected the drug from deactivation by gastric and intestinal fluids, maintained a high concentration in the intestinal tract and maximally kept the gut microbiota homeostasis. As such, this targeted antibiotic delivery systems are for the encapsulation of antibiotics to target specific enteropathogens.
Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: