Antibiotic-based micelles with bone-targeting and pH-responsive properties for infectious osteomyelitis treatment

We developed antibiotic-based micelles with bone-targeting and charge-switchable properties (P-CASMs) for treating infectious osteomyelitis. The amphiphilic molecules are formed by combining ciprofloxacin (CIP) with ligand 1 through a mild salifying reaction, and spontaneously self-assemble into antibiotic-based micelles (ASMs) in aqueous solution. Acrylate groups on ligand 1 enable cross-linking of ASMs with pentaerythritol tetra(mercaptopropionate) via a click reaction, forming pH-sensitive cross-linked micelles (CASMs). The incorporation of vinylphosphonates imparts bone-targeting and charge-switchable properties of CASMs, creating P-CASMs. These P-CASMs exhibit good biocompatibility at physiological pH and strong adhesion to bone infection sites (pH 5.5) due to electrostatic interactions. They can effectively penetrate bacterial biofilms and release antibiotics in response to the local microenvironment, thereby eradicating bacteria. Compared to previous systems, the P-CASMs show higher drug loading (∼23 %), improved stability, and better biosafety. This innovative system holds substantial potential for clinical applications in the treatment of osteomyelitis.