Min Li1, Koon Gee Neoh2, Liqun Xu1, Liang Yuan1, David Tai Leong1, En-Tang Kang1, Kim Lee Chua3, Li Yang Hsu4. 1. Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge,, Singapore, 117585, Singapore. 2. Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge,, Singapore, 117585, Singapore. chenkg@nus.edu.sg. 3. Department of Biochemistry, National University of Singapore, Kent Ridge,, Singapore, 117543, Singapore. 4. Department of Medicine, National University of Singapore, Kent Ridge, Singapore, 119228, Singapore.
Abstract
PURPOSE: The use of "Trojan Horse" nanocarriers for antibiotics to enhance the activity of antibiotics against susceptible and resistant bacteria is investigated. METHODS: Antibiotic carriers (CD-MAN and CD-GLU) are prepared from β-cyclodextrin grafted with sugar molecules (D-mannose and D-glucose, respectively) via azide-alkyne click reaction. The sugar molecules serve as a chemoattractant enticing the bacteria to take in higher amounts of the antibiotic, resulting in rapid killing of the bacteria. RESULTS: Three types of hydrophobic antibiotics, erythromycin, rifampicin and ciprofloxacin, are used as model drugs and loaded into the carriers. The minimum inhibitory concentration of the antibiotics in the CD-MAN-antibiotic and CD-GLU-antibiotic complexes for Gram-negative Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii strains, and a number of Gram-positive Staphylococcus aureus strains, including the methicillin-resistant strains (MRSA), are reduced by a factor ranging from 3 to >100. The CD-MAN-antibiotic complex is also able to prolong the stability of the loaded antibiotic and inhibit development of intrinsic antibiotic resistance in the bacteria. CONCLUSIONS: These non-cytotoxic sugar-modfied nanocarriers can potentiate the activity of existing antibiotics, especially against multidrug-resistant bacteria, which is highly advantageous in view of the paucity of new antibiotics in the pipeline.
PURPOSE: The use of "Trojan Horse" nanocarriers for antibiotics to enhance the activity of antibiotics against susceptible and resistant bacteria is investigated. METHODS: Antibiotic carriers (CD-MAN and CD-GLU) are prepared from β-cyclodextrin grafted with sugar molecules (D-mannose and D-glucose, respectively) via azide-alkyne click reaction. The sugar molecules serve as a chemoattractant enticing the bacteria to take in higher amounts of the antibiotic, resulting in rapid killing of the bacteria. RESULTS: Three types of hydrophobic antibiotics, erythromycin, rifampicin and ciprofloxacin, are used as model drugs and loaded into the carriers. The minimum inhibitory concentration of the antibiotics in the CD-MAN-antibiotic and CD-GLU-antibiotic complexes for Gram-negative Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii strains, and a number of Gram-positive Staphylococcus aureus strains, including the methicillin-resistant strains (MRSA), are reduced by a factor ranging from 3 to >100. The CD-MAN-antibiotic complex is also able to prolong the stability of the loaded antibiotic and inhibit development of intrinsic antibiotic resistance in the bacteria. CONCLUSIONS: These non-cytotoxic sugar-modfied nanocarriers can potentiate the activity of existing antibiotics, especially against multidrug-resistant bacteria, which is highly advantageous in view of the paucity of new antibiotics in the pipeline.
Authors: R Monina Klevens; Jonathan R Edwards; Chesley L Richards; Teresa C Horan; Robert P Gaynes; Daniel A Pollock; Denise M Cardo Journal: Public Health Rep Date: 2007 Mar-Apr Impact factor: 2.792