Polyaspartamide-based antimicrobials for combatting bacterial infections.

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Antimicrobial Research

Background:

• Antimicrobial resistance (AMR) is a growing global health threat.
• Synthetic antibacterial polymers offer advantages over natural antimicrobial peptides.
• Cationic polymers are being explored as novel antimicrobial agents.

Purpose of the Study:

• To synthesize and characterize a series of cationic polyaspartamides (PASP_nDA_m).
• To systematically investigate the antibacterial activity and biocompatibility of these polymers.
• To identify optimal polymer structures for combating bacterial infections.

Main Methods:

• Synthesis of polyaspartamides via ammonolysis of poly(β-benzyl-L-aspartate).
• Evaluation of antibacterial activity against *S. aureus* and *E. coli* (MIC determination).
• Assessment of biocompatibility and *in vivo* efficacy in a mouse skin infection model.

Main Results:

• All synthesized PASP_nDA_m polymers exhibited antibacterial activity.
• PASP₁₀DA₆ showed potent activity (MIC = 7.8 μg mL^-1) and high selectivity (SI = 96).
• Mechanism involves bacterial membrane disruption, leading to rapid killing and reduced resistance development.
• *In vivo* studies confirmed effective antibacterial action with negligible toxicity.

Conclusions:

• Cationic polyaspartamides are effective antibacterial agents.
• PASP₁₀DA₆ is a promising candidate for treating bacterial infections due to its potent activity, low toxicity, and novel mechanism.
• This study presents a viable strategy for developing new antimicrobial therapies to combat AMR.