# Breaking biofilm barriers in skin wounds: Membrane-Active antimicrobials in an era of resistance

## TL;DR

This paper explores membrane-active antimicrobials as a promising solution for treating chronic wounds complicated by biofilms and antimicrobial resistance.

## Contribution

The paper reviews novel membrane-active antimicrobials and their delivery strategies to improve biofilm eradication and clinical efficacy.

## Key findings

- Membrane-active antimicrobials disrupt biofilms through multiple mechanisms like membrane permeabilization and quorum sensing interference.
- Advanced delivery systems like nanoparticles and hydrogels enhance antimicrobial stability and efficacy.
- Further research is needed to fully realize the therapeutic potential of these agents.

## Abstract

Chronic wounds remain a significant challenge for healthcare systems worldwide, placing a considerable burden on both patients and resources. Their management is further complicated by the persistence of biofilm-forming bacteria and an escalating problem of antimicrobial resistance, both of which restrict the effectiveness of conventional therapies. Antimicrobial compounds with a rapid onset of action and activity that is not solely dependent on bacterial metabolism represent promising alternatives for bacterial and biofilm eradication. Among these, membrane-active antimicrobials (MAAs), including antimicrobial peptides, peptidomimetics, and other membrane-disrupting compounds, constitute a particularly interesting group of agents. Recent investigations have revealed diverse mechanisms through which MAAs compromise biofilm integrity, ranging from permeabilization of bacterial membranes to interference with quorum sensing and extracellular polymeric substances. Furthermore, pharmaceutical innovations such as nanoparticle-based carriers, hydrogel matrices, and scaffold-based delivery systems have shown potential to enhance MAA stability, optimize and prolong release profiles, improve antimicrobial and anti-biofilm efficacy, increase tissue penetration, and mitigate cytotoxicity concerns. By integrating insights from microbiology, materials science, and drug development, this short review aims to outline the challenges posed by biofilms in chronic wounds, appraise the antimicrobial and anti-biofilm activity of MAAs, and discuss how advanced delivery strategies might expand their clinical efficacy.

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•Membrane-active antimicrobials offer diverse anti-biofilm mechanisms to tackle antimicrobial resistance.•Pharmaceutical innovations can overcome their drawbacks and speed progress toward clinical use.•Deeper insight into their mechanisms and targets is essential for full therapeutic potential.

Membrane-active antimicrobials offer diverse anti-biofilm mechanisms to tackle antimicrobial resistance.

Pharmaceutical innovations can overcome their drawbacks and speed progress toward clinical use.

Deeper insight into their mechanisms and targets is essential for full therapeutic potential.