Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa

Objectives The aim of this study was to enhance the antimicrobial efficacy of a liposomal gentamicin formulation with gallium metal (Lipo-Ga-GEN) against clinical isolates of Pseudomonas aeruginosa. Methods Sputum isolates of P. aeruginosa from cystic fibrosis patients were used to determine the MIC...

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Veröffentlicht in:Journal of antimicrobial chemotherapy 2008-12, Vol.62 (6), p.1291-1297
Hauptverfasser: Halwani, M., Yebio, B., Suntres, Z. E., Alipour, M., Azghani, A. O., Omri, A.
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container_end_page 1297
container_issue 6
container_start_page 1291
container_title Journal of antimicrobial chemotherapy
container_volume 62
creator Halwani, M.
Yebio, B.
Suntres, Z. E.
Alipour, M.
Azghani, A. O.
Omri, A.
description Objectives The aim of this study was to enhance the antimicrobial efficacy of a liposomal gentamicin formulation with gallium metal (Lipo-Ga-GEN) against clinical isolates of Pseudomonas aeruginosa. Methods Sputum isolates of P. aeruginosa from cystic fibrosis patients were used to determine the MIC and MBC of Lipo-Ga-GEN. P. aeruginosa biofilms were formed and used to compare the minimum biofilm eradication concentration of the conventional drugs with that of Lipo-Ga-GEN. Quorum sensing (QS) molecule reduction of P. aeruginosa was determined by monitoring N-acyl homoserine lactone production using Agrobacterium tumefaciens reporter strain (A136). Viability of the cultured human lung epithelial cells (A549) was determined by Trypan Blue assay in order to assess Ga toxicity. Results MIC and MBC values indicated that gentamicin was more effective against a highly resistant strain of P. aeruginosa (PA-48913) when delivered as a Lipo-Ga-GEN formulation (256 mg/L free gentamicin versus 2 mg/L Lipo-Ga-GEN). Lipo-Ga-GEN was the only formulation that completely eradicated biofilms and blocked QS molecules at a very low concentration (0.94 mg/L gentamicin). The decrease in cell viability was less in A549 cells exposed to Lipo-Ga, suggesting that encapsulated Ga is safer. Conclusions The results clearly indicate that the Lipo-Ga-GEN formulation is more effective than gentamicin alone in eradicating antibiotic-resistant P. aeruginosa isolates growing in a planktonic or biofilm community.
doi_str_mv 10.1093/jac/dkn422
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E. ; Alipour, M. ; Azghani, A. O. ; Omri, A.</creator><creatorcontrib>Halwani, M. ; Yebio, B. ; Suntres, Z. E. ; Alipour, M. ; Azghani, A. O. ; Omri, A.</creatorcontrib><description>Objectives The aim of this study was to enhance the antimicrobial efficacy of a liposomal gentamicin formulation with gallium metal (Lipo-Ga-GEN) against clinical isolates of Pseudomonas aeruginosa. Methods Sputum isolates of P. aeruginosa from cystic fibrosis patients were used to determine the MIC and MBC of Lipo-Ga-GEN. P. aeruginosa biofilms were formed and used to compare the minimum biofilm eradication concentration of the conventional drugs with that of Lipo-Ga-GEN. Quorum sensing (QS) molecule reduction of P. aeruginosa was determined by monitoring N-acyl homoserine lactone production using Agrobacterium tumefaciens reporter strain (A136). Viability of the cultured human lung epithelial cells (A549) was determined by Trypan Blue assay in order to assess Ga toxicity. Results MIC and MBC values indicated that gentamicin was more effective against a highly resistant strain of P. aeruginosa (PA-48913) when delivered as a Lipo-Ga-GEN formulation (256 mg/L free gentamicin versus 2 mg/L Lipo-Ga-GEN). Lipo-Ga-GEN was the only formulation that completely eradicated biofilms and blocked QS molecules at a very low concentration (0.94 mg/L gentamicin). The decrease in cell viability was less in A549 cells exposed to Lipo-Ga, suggesting that encapsulated Ga is safer. Conclusions The results clearly indicate that the Lipo-Ga-GEN formulation is more effective than gentamicin alone in eradicating antibiotic-resistant P. aeruginosa isolates growing in a planktonic or biofilm community.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkn422</identifier><identifier>PMID: 18931388</identifier><identifier>CODEN: JACHDX</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Acyl-Butyrolactones - metabolism ; Agrobacterium tumefaciens ; Agrobacterium tumefaciens - growth &amp; development ; aminoglycosides ; Anti-Bacterial Agents - metabolism ; Anti-Bacterial Agents - pharmacology ; antibiotics ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Biofilms ; Biofilms - drug effects ; Biological and medical sciences ; Cell Line ; Cell Survival ; Comparative studies ; Cystic fibrosis ; Cystic Fibrosis - complications ; Drug Synergism ; Epithelial Cells - microbiology ; Gallium - metabolism ; Gallium - pharmacology ; Gentamicins - metabolism ; Gentamicins - pharmacology ; Humans ; Liposomes - metabolism ; Medical sciences ; Microbial Sensitivity Tests ; Microbial Viability ; Microbiology ; Pharmacology ; Pharmacology. Drug treatments ; Pseudomonas aeruginosa ; Pseudomonas aeruginosa - drug effects ; Pseudomonas aeruginosa - isolation &amp; purification ; Pseudomonas Infections - microbiology ; quorum sensing ; Sputum - microbiology ; toxicity ; Trypan Blue - metabolism</subject><ispartof>Journal of antimicrobial chemotherapy, 2008-12, Vol.62 (6), p.1291-1297</ispartof><rights>The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. 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E.</creatorcontrib><creatorcontrib>Alipour, M.</creatorcontrib><creatorcontrib>Azghani, A. O.</creatorcontrib><creatorcontrib>Omri, A.</creatorcontrib><title>Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Objectives The aim of this study was to enhance the antimicrobial efficacy of a liposomal gentamicin formulation with gallium metal (Lipo-Ga-GEN) against clinical isolates of Pseudomonas aeruginosa. Methods Sputum isolates of P. aeruginosa from cystic fibrosis patients were used to determine the MIC and MBC of Lipo-Ga-GEN. P. aeruginosa biofilms were formed and used to compare the minimum biofilm eradication concentration of the conventional drugs with that of Lipo-Ga-GEN. Quorum sensing (QS) molecule reduction of P. aeruginosa was determined by monitoring N-acyl homoserine lactone production using Agrobacterium tumefaciens reporter strain (A136). Viability of the cultured human lung epithelial cells (A549) was determined by Trypan Blue assay in order to assess Ga toxicity. Results MIC and MBC values indicated that gentamicin was more effective against a highly resistant strain of P. aeruginosa (PA-48913) when delivered as a Lipo-Ga-GEN formulation (256 mg/L free gentamicin versus 2 mg/L Lipo-Ga-GEN). Lipo-Ga-GEN was the only formulation that completely eradicated biofilms and blocked QS molecules at a very low concentration (0.94 mg/L gentamicin). The decrease in cell viability was less in A549 cells exposed to Lipo-Ga, suggesting that encapsulated Ga is safer. Conclusions The results clearly indicate that the Lipo-Ga-GEN formulation is more effective than gentamicin alone in eradicating antibiotic-resistant P. aeruginosa isolates growing in a planktonic or biofilm community.</description><subject>Acyl-Butyrolactones - metabolism</subject><subject>Agrobacterium tumefaciens</subject><subject>Agrobacterium tumefaciens - growth &amp; development</subject><subject>aminoglycosides</subject><subject>Anti-Bacterial Agents - metabolism</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>antibiotics</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Biofilms</subject><subject>Biofilms - drug effects</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell Survival</subject><subject>Comparative studies</subject><subject>Cystic fibrosis</subject><subject>Cystic Fibrosis - complications</subject><subject>Drug Synergism</subject><subject>Epithelial Cells - microbiology</subject><subject>Gallium - metabolism</subject><subject>Gallium - pharmacology</subject><subject>Gentamicins - metabolism</subject><subject>Gentamicins - pharmacology</subject><subject>Humans</subject><subject>Liposomes - metabolism</subject><subject>Medical sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>Microbial Viability</subject><subject>Microbiology</subject><subject>Pharmacology</subject><subject>Pharmacology. 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E.</au><au>Alipour, M.</au><au>Azghani, A. O.</au><au>Omri, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>62</volume><issue>6</issue><spage>1291</spage><epage>1297</epage><pages>1291-1297</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><coden>JACHDX</coden><abstract>Objectives The aim of this study was to enhance the antimicrobial efficacy of a liposomal gentamicin formulation with gallium metal (Lipo-Ga-GEN) against clinical isolates of Pseudomonas aeruginosa. Methods Sputum isolates of P. aeruginosa from cystic fibrosis patients were used to determine the MIC and MBC of Lipo-Ga-GEN. P. aeruginosa biofilms were formed and used to compare the minimum biofilm eradication concentration of the conventional drugs with that of Lipo-Ga-GEN. Quorum sensing (QS) molecule reduction of P. aeruginosa was determined by monitoring N-acyl homoserine lactone production using Agrobacterium tumefaciens reporter strain (A136). Viability of the cultured human lung epithelial cells (A549) was determined by Trypan Blue assay in order to assess Ga toxicity. Results MIC and MBC values indicated that gentamicin was more effective against a highly resistant strain of P. aeruginosa (PA-48913) when delivered as a Lipo-Ga-GEN formulation (256 mg/L free gentamicin versus 2 mg/L Lipo-Ga-GEN). Lipo-Ga-GEN was the only formulation that completely eradicated biofilms and blocked QS molecules at a very low concentration (0.94 mg/L gentamicin). The decrease in cell viability was less in A549 cells exposed to Lipo-Ga, suggesting that encapsulated Ga is safer. Conclusions The results clearly indicate that the Lipo-Ga-GEN formulation is more effective than gentamicin alone in eradicating antibiotic-resistant P. aeruginosa isolates growing in a planktonic or biofilm community.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>18931388</pmid><doi>10.1093/jac/dkn422</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Acyl-Butyrolactones - metabolism
Agrobacterium tumefaciens
Agrobacterium tumefaciens - growth & development
aminoglycosides
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
antibiotics
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biofilms
Biofilms - drug effects
Biological and medical sciences
Cell Line
Cell Survival
Comparative studies
Cystic fibrosis
Cystic Fibrosis - complications
Drug Synergism
Epithelial Cells - microbiology
Gallium - metabolism
Gallium - pharmacology
Gentamicins - metabolism
Gentamicins - pharmacology
Humans
Liposomes - metabolism
Medical sciences
Microbial Sensitivity Tests
Microbial Viability
Microbiology
Pharmacology
Pharmacology. Drug treatments
Pseudomonas aeruginosa
Pseudomonas aeruginosa - drug effects
Pseudomonas aeruginosa - isolation & purification
Pseudomonas Infections - microbiology
quorum sensing
Sputum - microbiology
toxicity
Trypan Blue - metabolism
title Co-encapsulation of gallium with gentamicin in liposomes enhances antimicrobial activity of gentamicin against Pseudomonas aeruginosa
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