Abstract

Successful treatment of skin infections requires eradication of biofilms found in up to 90 % of all chronic wounds, causing delayed healing and increased morbidity. We hypothesized that chitosan hydrogel boosts the activity of liposomally-associated membrane active antimicrobials (MAA) and could potentially improve bacterial and biofilm eradication. Therefore, liposomes (∼300 nm) bearing chlorhexidine (CHX; ∼50 μg/mg lipid) as a model MAA were incorporated into chitosan hydrogel. The novel CHX-liposomes-in-hydrogel formulation was optimized for skin therapy. It significantly inhibited the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced macrophage and almost completely reduced biofilm formation. Moreover, it reduced Staphylococcus aureus and Pseudomonas aeruginosa adherent bacterial cells in biofilm by 64.2–98.1 %. Chitosan hydrogel boosted the anti-inflammatory and antimicrobial properties of CHX.

Highlights

  • Antimicrobial resistance is currently a serious medical threat, espe­ cially because of the decelerated and unsuccessful pipeline of antimi­ crobial candidates (Hall et al, 2020)

  • Novel approaches for biofilm eradication and efficient wound therapy are urgently needed as skin and soft tissue infections are among the most common infections in humans (Poulakou, Lagou, & Tsiodras, 2019)

  • Among the most common bacteria embedded in wound matrices are Staphylococcus aureus and Pseudomonas aeruginosa (Balaure & Grume­ zescu, 2020; Kadam et al, 2019)

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Summary

Introduction

Antimicrobial resistance is currently a serious medical threat, espe­ cially because of the decelerated and unsuccessful pipeline of antimi­ crobial candidates (Hall et al, 2020). Novel approaches for biofilm eradication and efficient wound therapy are urgently needed as skin and soft tissue infections are among the most common infections in humans (Poulakou, Lagou, & Tsiodras, 2019). These infections exhibit a polymicrobial nature and cleaver, novel strategies to eradicate multiple bacteria are necessary for their treatment. Among the most common bacteria embedded in wound matrices are Staphylococcus aureus and Pseudomonas aeruginosa (Balaure & Grume­ zescu, 2020; Kadam et al, 2019) These bacteria display multiple mechanisms of resistance, rendering their eradication challenging. Several antimicrobial mechanisms are proposed for chitosan; its inter­ action with negatively charged bacterial membranes leading to possible

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