Antimicrobial and Anti-Inflammatory Effects of Polyethyleneimine-Modified Polydopamine Nanoparticles on a Burn-Injured Skin Model

Abstract

Chronic infections involving bacterial biofilms pose significant treatment challenges due to the resilience of biofilms against existing antimicrobials. Here, we introduce a nanomaterial-based platform for treating Staphylococcus epidermidis biofilms, both in isolation and within a biofilm-infected burn skin model. Our approach leverages biocompatible and photothermal polydopamine nanoparticles (PDNP), functionalized with branched polyethyleneimine (PEI) and loaded with the antibiotic rifampicin, to target bacteria dwelling within biofilms. A key innovation of our method is its ability to not only target planktonic S. epidermidis, but also effectively tackle biofilm-embedded bacteria. We demonstrated that PDNP-PEI interacts effectively with the bacterial surface, facilitating laser-activated photothermal eradication of planktonic S. epidermidis. In a 3D model of skin burn injury, PDNP-PEI demonstrates anti-inflammatory and reactive oxygen species (ROS)-scavenging effects, reducing inflammatory cytokine levels and promoting healing. The rifampicin-loaded PDNP-PEI (PDNP-PEI-Rif) platform further shows significant efficacy against bacteria inside biofilms. The PDNP-PEI-Rif retained its immunomodulatory activity and efficiently eradicated biofilms grown on our burn-injured 3D skin model, effectively addressing the challenges of biofilm-related infections. This achievement marks a significant advancement in infection management, with the potential for a transformative impact on clinical practice.