Mechanically Robust Dissolving Microneedles Made of Supramolecular Photosensitizers for Effective Photodynamic Bacterial Biofilm Elimination

Abstract

Bacterial biofilms pose severe threats to public health worldwide and are intractable by conventional antibiotic treatment. Antimicrobial photodynamic therapy (PDT) is emerging as a promising strategy for eradicating biofilms by virtue of low invasiveness, broad-spectrum antibacterial activity, and nondrug resistance. However, its practical efficacy is impeded by the low water solubility, severe aggregation, and poor penetration of photosensitizers (PSs) into the dense extracellular polymeric substances (EPS) of biofilms. Herein, we develop a dissolving microneedle (DMN) patch composed of a sulfobutylether-β-cyclodextrin (SCD)/tetra(4-pyridyl)-porphine (TPyP) supramolecular PS for enhanced biofilm penetration and eradication. The inclusion of TPyP into the SCD cavity can drastically inhibit the aggregation of TPyP, thereby allowing for nearly tenfold reactive oxygen species production and high photodynamic antibacterial efficacy. Moreover, the TPyP/SCD-based DMN (TSMN) possesses excellent mechanical performance that can easily pierce the EPS of biofilm with a penetration depth of ∼350 μm, enabling sufficient contact of TPyP with bacteria and optimal photodynamic elimination of bacterial biofilms. Furthermore, TSMN could efficiently eradicate Staphylococcus aureus biofilm infection in vivo with good biosafety. This study offers a promising platform for supramolecular DMN for efficient biofilm elimination and other PDTs.