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PEGylation of Tobramycin Improves Mucus Penetration and Antimicrobial Activity against Pseudomonas aeruginosa Biofilms in Vitro.
Mol Pharm. 2018 04 02; 15(4):1643-1652.MP

Abstract

Pseudomonas aeruginosa is the predominant pathogen in the persistent lung infections of cystic fibrosis (CF) patients among other diseases. One of the mechanisms of resistance of P. aeruginosa infections is the formation and presence of biofilms. Previously, we demonstrated that PEGylated-tobramycin (Tob-PEG) had superior antimicrobial activity against P. aeruginosa biofilms compared to tobramycin (Tob). The goal of this study was to optimize the method of PEGylation of Tob and assess its activity in an in vitro CF-like mucus barrier biofilm model. Tob was PEGylated using three separate chemical conjugation methods and analyzed by 1H NMR. A comparison of the Tob-PEG products from the different conjugation methods showed significant differences in the reduction of biofilm proliferation after 24 h of treatment. In the CF-like mucus barrier model, Tob-PEG was significantly better than Tob in reducing P. aeruginosa proliferation after only 5 h of treatment (p < 0.01). Finally, Tob-PEG caused a reduction in the number of surviving P. aeruginosa biofilm colonies higher than that of Tob (p < 0.0001). We demonstrate the significantly improved antimicrobial activity of Tob-PEG against P. aeruginosa biofilms compared to Tob using two PEGylation methods. Tob-PEG had better in vitro activity compared to that of Tob against P. aeruginosa biofilms growing in a CF-like mucus barrier model.

Authors+Show Affiliations

Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy , The University of Texas at Austin , Austin , Texas 78712 , United States.Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy , The University of Texas at Austin , Austin , Texas 78712 , United States.INSERM, U1070, UFR de Médecine Pharmacie , Université de Poitiers , 86073 Poitiers Cedex 9 , France.Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy , The University of Texas at Austin , Austin , Texas 78712 , United States.Division of Molecular Pharmaceutics and Drug Delivery, 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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29514003

Citation

Bahamondez-Canas, Tania F., et al. "PEGylation of Tobramycin Improves Mucus Penetration and Antimicrobial Activity Against Pseudomonas Aeruginosa Biofilms in Vitro." Molecular Pharmaceutics, vol. 15, no. 4, 2018, pp. 1643-1652.
Bahamondez-Canas TF, Zhang H, Tewes F, et al. PEGylation of Tobramycin Improves Mucus Penetration and Antimicrobial Activity against Pseudomonas aeruginosa Biofilms in Vitro. Mol Pharm. 2018;15(4):1643-1652.
Bahamondez-Canas, T. F., Zhang, H., Tewes, F., Leal, J., & Smyth, H. D. C. (2018). PEGylation of Tobramycin Improves Mucus Penetration and Antimicrobial Activity against Pseudomonas aeruginosa Biofilms in Vitro. Molecular Pharmaceutics, 15(4), 1643-1652. https://doi.org/10.1021/acs.molpharmaceut.8b00011
Bahamondez-Canas TF, et al. PEGylation of Tobramycin Improves Mucus Penetration and Antimicrobial Activity Against Pseudomonas Aeruginosa Biofilms in Vitro. Mol Pharm. 2018 04 2;15(4):1643-1652. PubMed PMID: 29514003.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PEGylation of Tobramycin Improves Mucus Penetration and Antimicrobial Activity against Pseudomonas aeruginosa Biofilms in Vitro. AU - Bahamondez-Canas,Tania F, AU - Zhang,Hairui, AU - Tewes,Frederic, AU - Leal,Jasmim, AU - Smyth,Hugh D C, Y1 - 2018/03/13/ PY - 2018/3/8/pubmed PY - 2019/3/16/medline PY - 2018/3/8/entrez KW - PEGylation KW - Pseudomonas aeruginosa KW - biofilm KW - cystic fibrosis KW - tobramycin SP - 1643 EP - 1652 JF - Molecular pharmaceutics JO - Mol Pharm VL - 15 IS - 4 N2 - Pseudomonas aeruginosa is the predominant pathogen in the persistent lung infections of cystic fibrosis (CF) patients among other diseases. One of the mechanisms of resistance of P. aeruginosa infections is the formation and presence of biofilms. Previously, we demonstrated that PEGylated-tobramycin (Tob-PEG) had superior antimicrobial activity against P. aeruginosa biofilms compared to tobramycin (Tob). The goal of this study was to optimize the method of PEGylation of Tob and assess its activity in an in vitro CF-like mucus barrier biofilm model. Tob was PEGylated using three separate chemical conjugation methods and analyzed by 1H NMR. A comparison of the Tob-PEG products from the different conjugation methods showed significant differences in the reduction of biofilm proliferation after 24 h of treatment. In the CF-like mucus barrier model, Tob-PEG was significantly better than Tob in reducing P. aeruginosa proliferation after only 5 h of treatment (p < 0.01). Finally, Tob-PEG caused a reduction in the number of surviving P. aeruginosa biofilm colonies higher than that of Tob (p < 0.0001). We demonstrate the significantly improved antimicrobial activity of Tob-PEG against P. aeruginosa biofilms compared to Tob using two PEGylation methods. Tob-PEG had better in vitro activity compared to that of Tob against P. aeruginosa biofilms growing in a CF-like mucus barrier model. SN - 1543-8392 UR - https://www.unboundmedicine.com/medline/citation/29514003/PEGylation_of_Tobramycin_Improves_Mucus_Penetration_and_Antimicrobial_Activity_against_Pseudomonas_aeruginosa_Biofilms_in_Vitro_ DB - PRIME DP - Unbound Medicine ER -