title: Improved Biofilm Antimicrobial Activity of Polyethylene Glycol Conjugated Tobramycin Compared to Tobramycin in Pseudomonas aeruginosa Biofilms.
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.
authors: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors: Ju
authors: J
authors: Du
authors: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors: H M H N
authors: HM
authors: Bandara
authors: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors: Ping
authors: P
authors: Du
authors: ‡Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors: Hui
authors: H
authors: Huang
authors: §College of Natural Sciences, The University of Texas at Austin, Austin, Texas 78712, United States.
authors: Khang
authors: K
authors: Hoang
authors: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors: Dang
authors: D
authors: Nguyen
authors: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors: Sri Vasudha
authors: SV
authors: Mogarala
authors: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.|∥Center for Infectious Disease, The University of Texas at Austin, Austin, Texas 78712, United States.
authors: Hugh D C
authors: HD
authors: Smyth
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011092:Polyethylene Glycols / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D014031:Tobramycin / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D011092:Polyethylene Glycols; D014031:Tobramycin
keywords: PEGylation; biofilm model; cystic fibrosis; minimum inhibitory concentration; planktonic