349133 Amphiphilic Synthetic Copolymer with Membrane-Disrupting Antibacterial Properties

Monday, November 4, 2013
Grand Ballroom B (Hilton)
Daniela Espinosa1, Mingming Ma2 and Robert Langer2, (1)Polytechnic University of Puerto Rico, San Juan, PR, (2)Massachusetts Institute of Technology, Cambridge, MA

There is an increasing need for antimicrobial compounds with less susceptible mechanisms to antibiotic resistance. Antibiotics target essential cell functions. With increased use, bacteria are likely to develop resistance and transfer these traits among different groups by means of mobile genetic elements. Cationic antimicrobial peptides circumvent the problem by physically binding and disrupting the negatively charged bacteria membrane, causing leakage of cell contents that leads to cell death. Synthetic polymers may interact with bacteria membrane by similar mechanisms with additional advantages: cost-effectivity for high scale production, compatibility with drug delivery methodology, and flexibility for chemical synthesis and modification. We designed and synthesized polymers with positive tags and investigated their membrane disrupting activity in calcein-encapsulated liposomes. Using a conventional broth dilution assay, an amphiphilic block copolymer was found to have a bacteriostatic effect in E. Coli with a minimum inhibitory concentration of 1 μM – lower than most currently used antibacterial peptides. Further experiments explored the minimal bactericidal concentration with an agar plate assay, and no bacteria growth occurred at 1 μM. Cytotoxicity in mammalian cells was tested with an XTT assay to determine its viability as an antimicrobial agent for medical devices and disinfecting applications. The assay with cervical cancer cells suggested greater than 90% viability at 50 μM, with 50:1 selectivity towards the bacteria. Further experiments will explore the polymer’s bactericidal capability against gram-positive and multidrug resistant bacteria.

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