Surface-Immobilized Antimicrobial Peptoids (28138)
Northwestern researchers have developed peptoid mimics of antimicrobial peptides that can be immobilized onto surfaces, rendering these surfaces capable of compromising the membranes of attached bacteria.
ADVANTAGES: Peptoids afford promising alternatives to conventional antimicrobials because of their stability, ease of synthesis and low cytotoxicity. These agents present solutions to infections associated with implantable medical devices.
SUMMARY: Surface-immobilized antimicrobial polymers applications include medical devices, water purification systems, food packaging, and hospital equipment. Bacterial infections on implanted medical devices such as catheters and pacemakers can lead to serious complications because the adherent bacteria can form a biofilm, which provides a protective environment against antibiotics and immune responses. Strategies to limit bacterial fouling of surfaces can incorporate either passive or active elements. Passive involve the use of antifouling polymer surface coatings to provide resistance to physical attachment of bacteria. Active surface coatings also contain components capable of killing bacteria through direct contact. Antimicrobial peptides (AMPs) offer activity against a wide range of organisms, while functioning with some selectivity for bacteria over mammalian cells. Peptoids are non-natural mimics of polypeptides well suited for antibacterial peptide use because they are resistant to protease enzymes.
Antimicrobial peptoid oligomers (ampetoids) designed to mimic helical antimicrobial peptides were synthesized. PMP1-AMP, a peptoid sequence composed of segments with low minimum inhibitory concentration (MIC) and high selectivity for bacterial versus mammalian cells, antifouling peptoids and adhesive peptides. PMP1-C containing a peptoid sequence exhibiting very low antibacterial and hemolytic activity, retaining the antifouling peptoids and adhesive peptides construct of PMP1-AMP as a control. PMP110, a shorter version of the antifouling peptoid and adhesive peptide construct used to ‘backfill’ the surfaces with a passive antifouling peptoid after modification with PMP1-AMP.
TiO2 slides modified with these polymers were exposed to E. coli suspensions, and remaining surface bacteria were imaged in phase contrast for determination of cell numbers, and in fluorescence after staining to detect cells with compromised membranes. Staining revealed the highest percentage of bacterial cells with damaged membranes on the active PMP1-AMP polymer surface when compared to PMP1-C, PMP110 treated and TiO2 surfaces (Table 1 ). Similar results are expected for B. subtilis, S. epidermidis and P. aeruginosa based on the MIC values determined for the ampetoids in solution.
The antifouling properties of treated TiO2 surfaces to 3T3-Swiss albino fibroblast adhesion was also demonstrated, (Figure 1). While the total projected area of adherent cells was greater on the polymer-modified surfaces containing the ampetoids than on the PMP110 substrates, all modified substrates had a significant reduction in cell adhesion compared to bare TiO2. The adherent cells also appeared to spread less on the ampetoid surfaces than the bare TiO,2 substrates. These novel peptoids are promising alternatives to conventional antimicrobials because of their stability, ease of synthesis, surface immobilization and low cytotoxicity. A broad range of medical and commercial applications are indicated.
STATUS: A patent application has been filed.
Table 1: Quantification of E. coli adhesion and membrane permeation on bare and modified TiO2 substrates. Standard deviations from the mean for nine images are reported.
Philip Messersmith and Annelise Barron
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