Cationic Polymers Based on a Polyester Backbone Possessing Potent Antimicrobial Activity against Drug-Resistant...

Area of Science:

• Polymer Chemistry
• Antimicrobial Materials
• Drug Discovery

Background:

• Multidrug resistance (MDR) infections present a significant threat to public health, diminishing the effectiveness of conventional antibiotics.
• Developing antimicrobial agents with potent efficacy, biocompatibility, and simplified structures is a critical unmet need.
• Host defense peptides (HDPs) offer a template for novel antimicrobial strategies due to their broad-spectrum activity and unique mechanisms.

Purpose of the Study:

• To design and synthesize a new class of cationic and amphiphilic polymers based on a simplified polyester backbone.
• To evaluate the antibacterial activity, biofilm eradication potential, and biocompatibility of these novel polymer structures.
• To explore the potential of these polymers as synthetic mimics of HDPs for combating MDR infections.

Main Methods:

• Synthesis of cationic and amphiphilic Poly(ε-caprolactone) (PCL) derivatives.
• Characterization of polymer structures and properties.
• In vitro assessment of broad-spectrum antibacterial activity, including against MDR strains.
• Evaluation of efficacy in eradicating mature bacterial biofilms.
• In vivo safety studies in mice.

Main Results:

• The optimal polymer, PKCL45, demonstrated broad-spectrum antibacterial activity at low concentrations (1 μg/mL).
• PKCL45 effectively eradicated mature bacterial biofilms and exhibited insusceptibility to multidrug resistance.
• In vivo studies in mice confirmed the systemic safety of the developed polymers.
• The polyester backbone successfully mimicked the function of hydrophobic amino acids in HDPs, simplifying polymer design.

Conclusions:

• Polyester-backbone antimicrobial polymers represent a promising new class of agents for combating bacterial infections, including MDR strains.
• The simplified, cationic, and amphiphilic polymer design offers a viable strategy for developing effective and biocompatible antimicrobials.
• These findings provide a novel approach for the clinical design of antimicrobial agents to address the challenge of antibiotic resistance.