Novel Biocompatible Hyaluronic Acid (HA)/Polyvinylpyrrolidone (PVP) Composites Containing Silver Decorated-Zinc MOF Nanoparticles: Antimicrobial Activity, Drug Delivery and Wound Healing

Abstract

Chronic infected wounds with multi-drug resistant pathogens present severe therapeutic challenges, often leading to prolonged morbidity and impaired healing. To address this, we engineered a multifunctional wound dressing by integrating Voriconazole-loaded silver/zinc MOFs (VOR@Ag/Zn-MOFs) into a hyaluronic acid/polyvinylpyrrolidone (HA/PVP) matrix. The composite was prepared through sequential steps, including preparing a HA/PVP polymer blend via solvent dissolution, synthesizing bimetallic Ag/Zn-MOFs through chemical precipitation, loading VOR into MOF nanocages, and consolidating the composite via chemical crosslinking followed by freeze-drying. Comprehensive physicochemical characterization to confirm MOF stability was implemented through SEM/EDX, confirming uniform nanocage architecture and elemental distribution (Ag/Zn/F), while DLS revealed controlled particle dimensions, and optimal colloidal stability (PDI 0.694; ZP + 39.3 mV). FTIR confirmed structural integrity through preserved polymer peaks (O–H 3400–3200, C = O 1650 cm⁻1), VOR-specific C-F (1400–1200 cm⁻1), and MOF Zn–O bonds (1100–1000/400–600 cm⁻1), verifying non-covalent integration without degradation. XRD further verified the crystalline framework integrity. In-vitro release studies demonstrated sustained biphasic release (44.2% ± 5.9 burst within 6 h; up to 77.1% ± 1.8 controlled release over 360 h). The composite demonstrated exceptional antimicrobial synergy, including potent antifungal activity against Candida albicans (MFC 1.4 µg/mL, 214-fold lower than free VOR) with microscopically-confirmed cell wall disruption, and broad bacteriostatic activity (MIC range 8,500–17,000 µg/mL against Gram-positive and Gram-negative pathogens). Critically, it achieved complete fungal clearance within 24 h. Simultaneously, it accelerated tissue regeneration, showing outstanding fibroblast biocompatibility (IC₃₀ > 3,000 µg/mL; 6,000-fold safety margin) and enabling marked wound closure within 72 h in the wound healing study. By converging triple-action mechanisms, including metal ion synergy (Ag⁺/Zn2⁺), targeted azole delivery, and HA/PVP-mediated pro-regenerative signaling, this platform uniquely eliminates resilient infections and restores wound integrity that was previously unattainable with conventional azole therapies.