Miconazole-splitomicin combined β-glucan hydrogel for effective prevention of Candida albicans periprosthetic joint infection

As one of the most common and serious infections caused by Candida albicans (C. albicans), periprosthetic joint infection (PJI) increasingly concerns surgeons and scientists. Generally, biofilms shield C. albicans from antifungal agents and immune clearance and induce drug-resistant strains. Developing novel strategies for PJI to get rid of current drug-resistant problems is highly needed. In our study, splitomicin (SP) can inhibit the mycelium formation of C. albicans and enhance the drug sensitivity of C. albicans to miconazole nitrate (MCZ). The combination of SP and MCZ significantly inhibited the viability, proliferation and adhesion of C. albicans, reduced the yeast to hyphae transition and biofilm formation. When SP and MCZ were coloaded in the β-glucan hydrogel, a viscoelastic solid with porous 3D network, sustained release and erosion properties was obtained. In the in vivo PJI mice model, SP-MCZ-β-glucan hydrogel effectively reduced the colonization and aggregation of C. albicans around the implant, reduced the pathological changes caused by C. albicans in the femur tissue. Therefore, SP-MCZ-β-glucan hydrogel holds a great promise for the management of C. albicans infection around joint prosthesis.