Biocompatible Rhamnolipid Self‐Assemblies with pH‐Responsive Antimicrobial Activity

There is an urgent need for alternative antimicrobial materials due to the growing challenge of bacteria becoming resistant to conventional antibiotics. This study demonstrates the creation of a biocompatible pH‐switchable antimicrobial material by combining bacteria‐derived rhamnolipids (RL) and food‐grade glycerol monooleate (GMO). The integration of RL into dispersed GMO particles, with an inverse‐type liquid crystalline cubic structure in the core, leads to colloidally stable supramolecular materials. The composition and pH‐triggered structural transformations are studied with small‐angle X‐ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering. The composition‐structure‐activity relationship is analyzed and optimized to target bacteria at acidic pH values of acute wounds. The new RL/GMO dispersions reduce Staphylococcus aureus (S. aureus) populations by 7‐log after 24 h of treatment with 64 µg mL−1 of RL and prevent biofilm formation at pH = 5.0, but have no activity at pH = 7.0. Additionally, the system is active against methicillin‐resistant S. aureus (MRSA) with minimum inhibitory concentration of 128 µg mL−1 at pH 5.0. No activity is found against several Gram‐negative bacteria at pH 5.0 and 7.0. The results provide a fundamental understanding of lipid self‐assembly and the design of lipid‐based biomaterials, which can further guide the development of alternative bio‐based solutions to combat bacteria. This study introduces a pH‐responsive antimicrobial nanomaterial made from bio‐derived rhamnolipids and glycerol monooleate. pH‐ and composition‐triggered colloidal transformations are reported and optimized for antimicrobial performance. The material kills Staphylococcus aureus and methicillin‐resistant Staphylococcus aureus at pH 5.0 but not at pH 7.0. Furthermore, it inhibits Staphylococcus aureus biofilm formation. The nanomaterial shown biocompatible with human dermal fibroblasts.