{"title":"Imipenem/cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates","authors":"Shakila Baei Lashaki , Pooria Moulavi , Fatemeh Ashrafi , Aram Sharifi , Sepideh Asadi","doi":"10.1016/j.jgar.2025.01.010","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>This study aims to investigate the effectiveness of UIO-66-NH<sub>2</sub>, a metal-organic framework, as a carrier for imipenem/cilastatin (Imp/Cil) in overcoming resistance in clinical isolates of imipenem-resistant <em>Pseudomonas aeruginosa</em>.</div></div><div><h3>Methods</h3><div>The UIO-66-NH<sub>2</sub>-Imp/Cil formulations were synthesized and characterized using dynamic light scattering, scanning electron microscopy, and transmission electron microscopy. Drug entrapment efficiency of UIO-66-NH<sub>2</sub>-Imp/Cil, and Imp/Cil release rates were determined. The stability of formulations was assessed at room temperature and refrigeration for two months. The antibacterial, anti-biofilm, and anti-virulence activities of formulations were investigated against imipenem-resistant <em>P. aeruginosa</em> isolates.</div></div><div><h3>Results</h3><div>The UIO-66-NH<sub>2</sub>-Imp/Cil formulation showed an average particle size of 212.3 ± 7.3 nm, a polydispersity index of 0.142 ± 0.010, and an entrapment efficiency (EE%) of 74.19% ± 1.12%. Drug release from the formulation followed a Korsmeyer-Peppas kinetic model, with 52% of the drug released over 72 h. Antibacterial testing indicated a significant decrease in minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the UIO-66-NH<sub>2</sub>-Imp/Cil formulation compared to free Imp/Cil, demonstrating enhanced antibacterial activity. Furthermore, the anti-biofilm and anti-virulence activity of UIO-66-NH<sub>2</sub>-Imp/Cil was confirmed by the reduction of bacterial haemolysis activity, minimal pyocyanin, EPS (extracellular polymeric substance) production, and lower metabolic activity of pathogens. Also, UIO-66-NH<sub>2</sub>-Imp/Cil causes significant reduction in the expression of <em>lasA, lasB</em> and, <em>rhlA</em> genes, which resulted in the inhibition of quorum-sensing system activity.</div></div><div><h3>Conclusions</h3><div>These findings indicate that UIO-66-NH<sub>2</sub>-Imp/Cil nanocarriers offer a promising new approach against multidrug-resistant Gram-negative pathogens, providing insights into potential mechanisms of antimicrobial action.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"42 ","pages":"Pages 15-27"},"PeriodicalIF":3.2000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of global antimicrobial resistance","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213716525000177","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/30 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Background
This study aims to investigate the effectiveness of UIO-66-NH2, a metal-organic framework, as a carrier for imipenem/cilastatin (Imp/Cil) in overcoming resistance in clinical isolates of imipenem-resistant Pseudomonas aeruginosa.
Methods
The UIO-66-NH2-Imp/Cil formulations were synthesized and characterized using dynamic light scattering, scanning electron microscopy, and transmission electron microscopy. Drug entrapment efficiency of UIO-66-NH2-Imp/Cil, and Imp/Cil release rates were determined. The stability of formulations was assessed at room temperature and refrigeration for two months. The antibacterial, anti-biofilm, and anti-virulence activities of formulations were investigated against imipenem-resistant P. aeruginosa isolates.
Results
The UIO-66-NH2-Imp/Cil formulation showed an average particle size of 212.3 ± 7.3 nm, a polydispersity index of 0.142 ± 0.010, and an entrapment efficiency (EE%) of 74.19% ± 1.12%. Drug release from the formulation followed a Korsmeyer-Peppas kinetic model, with 52% of the drug released over 72 h. Antibacterial testing indicated a significant decrease in minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the UIO-66-NH2-Imp/Cil formulation compared to free Imp/Cil, demonstrating enhanced antibacterial activity. Furthermore, the anti-biofilm and anti-virulence activity of UIO-66-NH2-Imp/Cil was confirmed by the reduction of bacterial haemolysis activity, minimal pyocyanin, EPS (extracellular polymeric substance) production, and lower metabolic activity of pathogens. Also, UIO-66-NH2-Imp/Cil causes significant reduction in the expression of lasA, lasB and, rhlA genes, which resulted in the inhibition of quorum-sensing system activity.
Conclusions
These findings indicate that UIO-66-NH2-Imp/Cil nanocarriers offer a promising new approach against multidrug-resistant Gram-negative pathogens, providing insights into potential mechanisms of antimicrobial action.
期刊介绍：
The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes.
JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR).
Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.
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