In vitro antifungal and antibiofilm evaluation of reduction-responsive ketoconazole-loaded nanoparticles based on cystamine-modified poly (isobutene-alt-maleic anhydride) polymer

Purpose In order to develop reduction-responsive nano-drug delivery system for encapsulating antifungal drugs.Methods Herein, with poly (isobutene-alt-maleic anhydride) as skeleton, we synthesized a polymer containing cross-linked disulfide bonds to prepare reduction-responsive ketoconazole-loaded nanoparticles (MPEG-P-KET). The in vitro reduction-responsive behavior and antifungal activity of MPEG-P-KET were investigated.Results The MPEG-P-KET improved the dispersion and solubility of lipophilic KET. KET’s imidazole group formed a salt with the free carboxyl groups in the polymer carrier, resulting in delayed drug release from MPEG-P-KET. However, MPEG-P-KET still exhibited reduction-sensitive drug release behavior, and showed comparable antifungal activity with KET in vitro. Interestingly, MPEG-P-KET demonstrated higher ability to inhibit biofilm formation and disrupt mature biofilms than KET.Conclusion The polymeric nanoparticles with disulfide bonds could be used for the encapsulation and controlled delivery of antifungal drugs in the field of fungal infection treatment.