Imipenem/cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates
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 synthesi...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Journal of Global Antimicrobial Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716525000177 |
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| author | Shakila Baei Lashaki Pooria Moulavi Fatemeh Ashrafi Aram Sharifi Sepideh Asadi |
| author_facet | Shakila Baei Lashaki Pooria Moulavi Fatemeh Ashrafi Aram Sharifi Sepideh Asadi |
| author_sort | Shakila Baei Lashaki |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d29d24351e9d4dc0b7ee9d520fe4470c |
| institution | DOAJ |
| issn | 2213-7165 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj-art-d29d24351e9d4dc0b7ee9d520fe4470c2025-08-20T02:57:53ZengElsevierJournal of Global Antimicrobial Resistance2213-71652025-05-0142152710.1016/j.jgar.2025.01.010Imipenem/cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolatesShakila Baei Lashaki0Pooria Moulavi1Fatemeh Ashrafi2Aram Sharifi3Sepideh Asadi4Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, IranDepartment of Biology, North Tehran Branch, Islamic Azad University, Tehran, IranDepartment of Biology, North Tehran Branch, Islamic Azad University, Tehran, IranDepartment of Animal Science, Faculty of Agriculture, University of Kurdistan, Sanandaj, Kurdistan, IranDepartment of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, IranBackground: 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.http://www.sciencedirect.com/science/article/pii/S2213716525000177Antibacterial agentsBiofilmImipenem/cilastatinUio-66-NH2Pseudomonas aeruginosa |
| spellingShingle | Shakila Baei Lashaki Pooria Moulavi Fatemeh Ashrafi Aram Sharifi Sepideh Asadi Imipenem/cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates Journal of Global Antimicrobial Resistance Antibacterial agents Biofilm Imipenem/cilastatin Uio-66-NH2 Pseudomonas aeruginosa |
| title | Imipenem/cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates |
| title_full | Imipenem/cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates |
| title_fullStr | Imipenem/cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates |
| title_full_unstemmed | Imipenem/cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates |
| title_short | Imipenem/cilastatin encapsulation in UIO-66-NH2 carrier as a new strategy for combating imipenem-resistant Pseudomonas aeruginosa isolates |
| title_sort | imipenem cilastatin encapsulation in uio 66 nh2 carrier as a new strategy for combating imipenem resistant pseudomonas aeruginosa isolates |
| topic | Antibacterial agents Biofilm Imipenem/cilastatin Uio-66-NH2 Pseudomonas aeruginosa |
| url | http://www.sciencedirect.com/science/article/pii/S2213716525000177 |
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