Polymer-Antimicrobial Peptide Constructs with Tailored Drug-Release Behavior.

Area of Science:

• Biochemistry
• Materials Science
• Microbiology

Background:

• Antimicrobial peptides (AMPs) offer a novel strategy against microbial resistance.
• Clinical application of AMPs is limited by stability, toxicity, and immunogenicity.
• Polymer-peptide constructs aim to improve AMP delivery and efficacy.

Purpose of the Study:

• To design, synthesize, and evaluate polymer-antibacterial peptide constructs.
• To investigate pH-sensitive and enzymatically-driven release mechanisms for AMPs.
• To assess the antibacterial activity of polymer-AMP constructs against resistant bacteria.

Main Methods:

• Synthesis of polymer-oligopeptide constructs using biodegradable spacers.
• Determination of minimum inhibitory concentrations (MICs).
• Fluorescence and transmission electron microscopy (TEM) for mechanism analysis.

Main Results:

• The oligopeptide (PEP) demonstrated antibacterial activity against Gram-positive and Gram-negative bacteria by disrupting cell walls.
• PEP retained partial antibacterial efficacy against *Staphylococcus epidermidis*, *Escherichia coli*, and *Acinetobacter baumanii* when polymer-bound.
• pH-sensitive release of PEP at decreased pH restored antibacterial activity comparable to free PEP.
• Enzymatically-driven release was less effective than pH-sensitive release.

Conclusions:

• Polymer-AMP constructs offer a viable approach to enhance antimicrobial peptide delivery.
• pH-sensitive release is a more effective strategy for reactivating AMPs compared to enzymatic release.
• This approach holds potential for developing new treatments against drug-resistant microbial infections.