Stimuli-responsive dual-drug loaded microspheres with differential drug release for antibacterial and wound repair promotion

The healing of infected wounds is a complex and dynamic process requiring tailored treatment strategies that address both antimicrobial and reparative needs. Despite the development of numerous drugs, few approaches have been devised to optimize the timing of drug release for targeting distinct phases of infection control and tissue repair, limiting the overall treatment efficacy. Here, a stimuli-responsive microsphere encapsulating dual drugs was developed to facilitate differential drug release during distinct phases of antibacterial and repair promotion, thereby synergistically enhancing wound healing. Specifically, zeolite imidazolate backbone in poly (lactic-co-glycolic acid) (PLGA) microsphere was employed for the encapsulation of ciprofloxacin (CIP), responding to acidic environment of bacteria and releasing antibiotic for antibacterial therapy. Meanwhile, curcumin (CUR) encapsulated in PLGA exhibited a gradual release profile, contributing to synergistic antibacterial effects. During the tissue repair phase, near-infrared light stimulation of Fe₃O₄ embedded in PLGA generated heat, elevating the temperature to the glass transition point of PLGA, which significantly enhanced the release of CUR thereby promoting tissue repair. In vitro experiments demonstrated that the release of CIP and CUR achieved significant antibacterial effects in the early stages of treatment. Additionally, CUR could effectively enhance fibroblast migration and proliferation. In vivo studies using a mouse abscess model revealed that the microspheres exhibited remarkable antibacterial and wound-healing capabilities, effectively enhancing the re-epithelialization of wound tissue and reducing the infiltration of inflammatory cells. This study provides novel strategies for constructing drug delivery systems that match dynamic stages of wound healing, offering improved therapeutic outcomes for infected wounds.