End-Group Engineering in Amphiphilic Segmented Polyurethanes: Strong Impact on Hierarchical Self-Assembled Structure...

Area of Science:

• Polymer Chemistry
• Materials Science
• Antimicrobial Agents

Background:

• Amphiphilic polymers are versatile materials for drug delivery and biomedical applications.
• Developing novel antimicrobial agents with high efficacy and low toxicity is a critical need.
• Understanding structure-activity relationships in polymers is key to designing effective therapeutics.

Purpose of the Study:

• To synthesize and characterize novel amphiphilic polyurethanes with tunable properties.
• To investigate the self-assembly behavior and structural characteristics of these polymers.
• To evaluate the antibacterial activity, mammalian cell toxicity, and biofilm eradication potential of the synthesized polymers.

Main Methods:

• Condensation polymerization of hexyl-diisocyanate and Boc-protected serinol with various chain-stoppers.
• Boc deprotection to yield amphiphilic polymers with pendant amine groups.
• Characterization of polymer structure, self-assembly into vesicles, and surface properties.
• Minimum inhibitory concentration (MIC) assays against *E. coli* and *S. aureus*.
• Mammalian cell toxicity (HC50) assays.
• Biofilm eradication assays.

Main Results:

• Amphiphilic polyurethanes self-assembled into unilamellar vesicles with surface-displayed amine groups.
• Hydrophobic chain-stoppers significantly enhanced antibacterial activity by disrupting bacterial membranes.
• Increased hydrocarbon chain length (C5 to C8) dramatically reduced MIC values for *E. coli* and *S. aureus*.
• Polymers exhibited negligible toxicity toward mammalian cells (HC50 > 300 μg/mL).
• Hydrophilic chain-stoppers and excessively long hydrophobic chain-stoppers reduced antibacterial efficacy.
• The lead candidate demonstrated highly effective biofilm eradication.

Conclusions:

• The hierarchical assembly of amphiphilic polyurethanes leads to structures with potent antibacterial properties.
• Surface exposure of hydrophobic chains is crucial for antibacterial activity and bacterial membrane disruption.
• These polymers represent a promising class of antimicrobial agents with a favorable safety profile and biofilm eradication capabilities.