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Mol Pharm. 2015 May 4;12(5):1544-53. doi: 10.1021/mp500846u. Epub 2015 Apr 2.

Improved Biofilm Antimicrobial Activity of Polyethylene Glycol Conjugated Tobramycin Compared to Tobramycin in Pseudomonas aeruginosa Biofilms.

Author information

1
†Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
2
‡Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
3
§College of Natural Sciences, The University of Texas at Austin, Austin, Texas 78712, United States.
4
∥Center for Infectious Disease, The University of Texas at Austin, Austin, Texas 78712, United States.

Abstract

The objective of this study was to develop a functionally enhanced antibiotic that would improve the therapeutic activity against bacterial biofilms. Tobramycin was chemically conjugated with polyethylene glycol (PEG) via site-specific conjugation to form PEGylated-tobramycin (Tob-PEG). The antibacterial efficacy of Tob-PEG, as compared to tobramycin, was assessed on the planktonic phase and biofilms phase of Pseudomonas aeruginosa. The minimum inhibitory concentration (MIC80) of Tob-PEG was higher (13.9 μmol/L) than that of tobramycin (1.4 μmol/L) in the planktonic phases. In contrast, the Tob-PEG was approximately 3.2-fold more effective in eliminating bacterial biofilms than tobramycin. Specifically, Tob-PEG had a MIC80 lower than those exhibited by tobramycin (27.8 μmol/L vs 89.8 μmol/L). Both confocal laser scanning microscopy and scanning electron microscopy further confirmed these data. Thus, modification of antimicrobials by PEGylation appears to be a promising approach for overcoming the bacterial resistance in the established biofilms of Pseudomonas aeruginosa.

KEYWORDS:

PEGylation; biofilm model; cystic fibrosis; minimum inhibitory concentration; planktonic

PMID:
25793309
DOI:
10.1021/mp500846u
[Indexed for MEDLINE]

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