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<p>This study reports the successful synthesis and detailed physicochemical and biological characterization of novel nanochitosan (CHI) formulations co-loaded with curcumin (CUR) and lycopene (LYC) (CHI-CUR-LYC) for enhanced wound healing. The work mechanistically investigated how the incorporation of these two distinct bioactive agents modulates the structural, rheological, and therapeutic properties of the chitosan nanocarriers. Physicochemical analysis revealed that while single-loading with lycopene (CHI-LYC) promoted the formation of small (150.2&#xa0;nm), highly ordered, and crystalline nanoparticles with low polydispersity (PDI 0.243), co-loading in CHI-CUR-LYC resulted in a more amorphous structure (296.7&#xa0;nm, PDI 0.540). This structural difference, confirmed by XRD and FTNIR, is attributed to competitive hydrophobic packing between the two bioactives, which favorably leads to increased structural disorder beneficial for drug release. Rheological analysis confirmed that the CHI-CUR-LYC composite exhibited superior viscoelasticity and thixotropy due to synergistic network reinforcement, optimizing its applicability as a topical gel. The nanocarrier demonstrated superior bioactivity through a synergistic mechanism. The CHI-CUR-LYC formulation displayed the highest antioxidant capacity (74% DPPH scavenging) due to the complementary radical-quenching pathways of curcumin (Hydrogen Atom Transfer) and lycopene (Singlet Oxygen Quenching). It also exhibited potent, dose-dependent antibacterial activity against <i>S. aureus</i> and <i>E. coli</i>, driven by the combined membrane-disrupting action of chitosan and the cytotoxic effects of the encapsulated bioactives. In vitro release kinetics followed a non-Fickian anomalous transport model, ensuring sustained release over 50&#xa0;h (R<sup>2</sup> &gt; 0.93). Crucially, in a rat wound model, topical application of the CHI-CUR-LYC formulation led to significantly accelerated wound closure and complete epithelialization. Histological examination confirmed the superior therapeutic outcome, showing robust granulation tissue formation, enhanced angiogenesis, and well-organized collagen deposition. These results validate the rational design of the CHI-CUR-LYC composite, demonstrating its potential as a multifunctional nanodrug that leverages synergistic bioactivity and controlled release for advanced wound care applications.</p> Graphical Abstract <p></p>

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In Vitro and In Vivo Studies of Skin Wound Healing Potential of Nanochitosan Grafted Curcumin and Lycopene in Wistar Albino Rats

  • 期刊论文

  • 发表日期：

    2025年11月12日

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  • Sanjana Paddambail,
  • Jayashree Sadasivam,
  • Rangasamy Anandan,
  • Pavan Kumar Dara,
  • Sharadamma Narayanaswamy

摘要

This study reports the successful synthesis and detailed physicochemical and biological characterization of novel nanochitosan (CHI) formulations co-loaded with curcumin (CUR) and lycopene (LYC) (CHI-CUR-LYC) for enhanced wound healing. The work mechanistically investigated how the incorporation of these two distinct bioactive agents modulates the structural, rheological, and therapeutic properties of the chitosan nanocarriers. Physicochemical analysis revealed that while single-loading with lycopene (CHI-LYC) promoted the formation of small (150.2 nm), highly ordered, and crystalline nanoparticles with low polydispersity (PDI 0.243), co-loading in CHI-CUR-LYC resulted in a more amorphous structure (296.7 nm, PDI 0.540). This structural difference, confirmed by XRD and FTNIR, is attributed to competitive hydrophobic packing between the two bioactives, which favorably leads to increased structural disorder beneficial for drug release. Rheological analysis confirmed that the CHI-CUR-LYC composite exhibited superior viscoelasticity and thixotropy due to synergistic network reinforcement, optimizing its applicability as a topical gel. The nanocarrier demonstrated superior bioactivity through a synergistic mechanism. The CHI-CUR-LYC formulation displayed the highest antioxidant capacity (74% DPPH scavenging) due to the complementary radical-quenching pathways of curcumin (Hydrogen Atom Transfer) and lycopene (Singlet Oxygen Quenching). It also exhibited potent, dose-dependent antibacterial activity against S. aureus and E. coli, driven by the combined membrane-disrupting action of chitosan and the cytotoxic effects of the encapsulated bioactives. In vitro release kinetics followed a non-Fickian anomalous transport model, ensuring sustained release over 50 h (R2 > 0.93). Crucially, in a rat wound model, topical application of the CHI-CUR-LYC formulation led to significantly accelerated wound closure and complete epithelialization. Histological examination confirmed the superior therapeutic outcome, showing robust granulation tissue formation, enhanced angiogenesis, and well-organized collagen deposition. These results validate the rational design of the CHI-CUR-LYC composite, demonstrating its potential as a multifunctional nanodrug that leverages synergistic bioactivity and controlled release for advanced wound care applications.

Graphical Abstract