Nitric oxide-releasing poly(ionic liquid)-based microneedle for subcutaneous fungal infection treatment.

Poor permeation of therapeutic agents and similar eukaryotic cell metabolic and physiological properties of fungi and human cells are two major challenges that lead to the failure of current therapy for fungi-induced skin and soft tissue infections. Herein, a nitric oxide (NO)-releasing poly(ionic liquid)-based microneedle (PILMN-NO) with the capacity of deep persistent NO toward subcutaneous fungal bed is presented as a synergistic antifungal treatment strategy to treat subcutaneous fungal infection. Upon the insertion of PILMN-NO into skin, the contact fungicidal activities induced by electrostatic and hydrophobic effects of poly(ionic liquid) and the released NO sterilization resulting from the peroxidation and nitrification effect of NO achieved enhanced antifungal efficacy against fungi ( Candida albicans ) both in vitro and in vivo . Simultaneously, PILMN-NO showed biofilm ablation ability and efficiently eliminated mature biofilms. In vivo fungal-induced subcutaneous abscess studies revealed that PILMN-NO could effectively sterilize fungi while suppressing the inflammatory reaction, facilitating collagen deposition and angiogenesis, and promoting wound healing. This work provides a new strategy to overcome the difficulties in deep skin fungal infection treatment and has potential for further exploitation of NO-releasing microbicidal therapy.