Triclosan-conjugated, Lipase-responsive Polymeric Micelles for Eradication of Staphylococcal Biofilms

Bacterial biofilms present a significant challenge in treating drug-resistant infections, necessitating the development of innovative nanomedicines. In this study, we introduce triclosan-conjugated, lipase-responsive polymeric micelles designed to exploit biofilm properties and serve as a responsive drug delivery platform. The micelles were created using an amphiphilic block polymer synthesized via ring-opening polymerization of ε-caprolactone (CL) and triclosan-containing cyclic trimethylene carbonate (MTC-Tri). Poly(ethylene glycol) (PEG-OH) acted as the macro-initiator, resulting in micelles with a PEG shell that facilitated their penetration into bacterial biofilms. An important advantage of our micelles lies in their interaction with local bacterial lipases within biofilms. These lipases triggered rapid micelle degradation, releasing triclosan in a controlled manner. This liberated triclosan effectively eliminated bacteria embedded in the biofilms. Notably, the triclosan-conjugated micelles displayed minimal toxicity to murine fibroblasts, indicating their biocompatibility and safety. This finding emphasizes the potential application of these micelles in combatting drug resistance observed in bacterial biofilms. Our triclosan-conjugated, lipase-responsive polymeric micelles exhibit promising characteristics for addressing drug resistance in bacterial biofilms. By harnessing biofilm properties and implementing a responsive drug delivery system, we seek to provide an effective solution in the fight against drug-resistant bacteria.