Iron-curcumin-carboxy PTIO coordinated nanoparticles with anti-inflammatory properties for enhanced diabetic wound healing

Introduction Diabetic wounds present major healing challenges due to chronic inflammation and oxidative stress. Conventional antioxidants like curcumin are limited by poor solubility and bioavailability. Methods We developed iron-curcumin-coordinated nanoparticles (Fe-Cur-P) to harness curcumin's antioxidant effects while improving its solubility and biocompatibility via iron coordination. The nanoparticles were characterized for size, drug loading, and pH-responsive release of carboxy-PTIO (a nitric oxide scavenger). Antioxidant activity was evaluated using DPPH·, ABTS+·, and methylene blue assays. In vitro anti-inflammatory effects were assessed in LPS-stimulated RAW 264.7 macrophages by measuring apoptosis and cytokine expression. In vivo efficacy was tested in a diabetic mouse wound model, with wound closure rate, histology, and immunohistochemistry analyzed. Results The Fe-Cur-P nanoparticles exhibited a uniform size (9.8 ± 0.6 nm) with 21.31% drug loading and enabled pH-responsive carboxy-PTIO release in acidic wound environments. They potently scavenged reactive oxygen and nitrogen species in multiple antioxidant assays. In RAW 264.7 macrophages, Fe-Cur-P reduced LPS-induced apoptosis and significantly suppressed pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α, and COX-2. In diabetic mice, Fe-Cur-P accelerated wound closure (93.5% ± 2.4% by day 14), promoted vascularization and collagen deposition, and upregulated TGF-β while attenuating inflammation, outperforming both untreated controls and free curcumin. Discussion Iron-curcumin-coordinated nanoparticles effectively combine enhanced curcumin bioavailability with targeted antioxidant and anti-inflammatory activities, demonstrating significant therapeutic potential for diabetic wound healing. This nanoplatform offers a promising strategy to address the multifactorial impairments in chronic wounds.