Functional Self-Similar Polyether-Polyester Mimicking Host Defense Peptides Enable Prolonged Antimicrobial Activity

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Antimicrobial Research

Background:

• Chronic wounds are susceptible to bacterial infections, necessitating long-term antimicrobial treatments.
• Host defense peptides (HDPs) and cationic polymers show antimicrobial promise but are often degraded by proteases, limiting their efficacy.
• Developing stable antimicrobial agents is crucial for combating drug-resistant bacteria in chronic wound settings.

Purpose of the Study:

• To design and synthesize novel cationic polyether-polyester-mimicking polymers with sustained antimicrobial activity.
• To evaluate the antimicrobial efficacy, biocompatibility, and stability of these polymers against protease-mediated degradation.
• To explore the potential of these functional self-similar polymers for treating chronic wound infections.

Main Methods:

• Synthesis of a series of cationic polyether-polyester-mimicking copolymers.
• Antimicrobial activity testing against various bacteria, including determination of minimum inhibitory concentrations (MICs).
• Enzymatic degradation studies to assess polymer stability and retained activity.
• In vivo evaluation of antibacterial performance and safety in mouse models.

Main Results:

• The optimal copolymer, P8, demonstrated broad-spectrum antimicrobial activity with MICs as low as 0.5 μg/mL.
• P8 maintained significant antimicrobial activity after enzymatic degradation, with an MIC of 16 μg/mL.
• The rational design of the copolymer backbone and hydrophobic side chains contributed to superior performance.
• P8 exhibited potent in vivo antibacterial efficacy and excellent safety in mouse models.

Conclusions:

• Functional self-similar polymers offer a promising strategy for developing long-lasting antimicrobial agents.
• These polymers effectively address the challenge of protease-mediated degradation, enhancing therapeutic potential.
• The developed materials show potential for clinical applications in treating bacterial resistance and chronic wound infections with prolonged, low-toxicity antibacterial therapies.