Enhanced antimicrobial protection through surface immobilization of antibiotic-loaded peptide multicompartment micelles

The escalating global threat of antibiotic-resistant bacterial infections, driven by biofilm formation on medical device surfaces, prompts the need for innovative therapeutic strategies. To address this growing challenge, we develop rifampicin-loaded multicompartment micelles (RIF-MCMs) immobilized on surfaces, offering a dual-functional approach to enhance antimicrobial efficacy for localized therapeutic applications. We first optimize the physicochemical properties of RIF-MCMs, and subsequently coat the optimal formulation onto a glass substrate, as confirmed by quartz crystal microbalance and atomic force microscopy. Surface-immobilized RIF-MCMs facilitate sustained antibiotic release in response to biologically relevant temperatures (37 °C and 42 °C). In addition, their heterogeneous distribution enhances the surface's roughness, contributing to the antibacterial activity through passive mechanisms such as hindering bacterial adhesion and biofilm formation. <i>In vitro</i> antimicrobial testing demonstrates that RIF-MCM-modified surfaces achieve a 98% reduction in <i>Staphylococcus aureus</i> viability and a three-order-of-magnitude decrease in colony formation compared to unmodified surfaces. In contrast, RIF-MCMs exhibit minimal cytotoxicity to mammalian cells, making them suitable candidates for medical device coatings. Our dual-function antimicrobial strategy, combining sustained antibiotic release and enhanced surface roughness, presents a promising approach to locally prevent implant-associated infections and biofilm formation.