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Purpose <p>Hesperidin (HES) has myriad biological activities that may expedite the wound healing rate. However, the poor aqueous solubility, stability, and bioavailability of HES limit its application. Therefore, a formulation that can address these issues and facilitate its sustained release at the wounded site may be beneficial. In this work, a sesame seed oil-enriched nanostructured lipid carrier hydrogel of HES was prepared and evaluated for its wound healing potential.</p> Methods <p>HES-loaded nanostructured lipid carrier (HES-NLCs) were prepared using the hot-homogenization and ultrasonication method. Box-Behnken Design and numerical optimization approach were employed to obtain the optimal formulation. Subsequently, the optimized HES-NLC (OHES-NLC) was loaded into a hydrogel (OHES-NLCG) and characterized. In addition, OHES-NLCG was assessed for the in-vitro drug release, anti-oxidant (DPPH assay), in-vivo wound contraction (full-thickness excisional wound model in rats), and skin irritation (Draize’s primary skin irritation model) potential.</p> Results <p>The OHES-NLC with an overall desirability value of 0.90 showed particles in the nanosize range (198.7&#xa0;nm), narrow distribution (PDI = 0.26), high stability (zeta potential = -29.11 mV), and reasonable percent drug entrapment efficiency (65.23%). Furthermore, OHES-NLCG showed good skin compatibility, and significantly higher (<i>p</i> &lt; 0.05) in-vitro drug permeation (85.80 ± 6.20% vs. 35.61 ± 5.59%) for HES compared to HES-loaded conventional gel (HES-CG). The HES release from the OHES-NLCG followed the Higuchi model (R<sup>2</sup> = 0.9869). Moreover, the % DPPH scavenging for OHES-NLCG was significantly higher (<i>p</i> &lt; 0.05) vis-à-vis HES-CG (IC<sub>50</sub> value of 34.25 ± 1.3 vs. 67.83 ± 3.2&#xa0;µg / mL). In addition, OHES-NLCG-treated Wistar rats showed a 94.03 ± 3.28% wound area closure compared to 47.35 ± 4.56% for the untreated rats after 14 days of the wound induction (<i>p</i> &lt; 0.05).</p> Conclusion <p>Hence, the outcomes of the study revealed that OHES-NLCG has a promising wound-healing activity in a full-thickness excisional wound model in rats, warranting further detailed investigations.</p> Graphical Abstract <p></p>

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Box-Behnken Enabled Development and Optimization of Polyunsaturated Fatty Acid Enriched Nano Gel of Hesperidin for Augmented Anti-oxidant and Wound Healing Potential

  • 期刊论文

  • 发表日期：

    2026年3月19日

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  • Shashank Chaturvedi,
  • Richa Sharma,
  • Ahsas Goyal

摘要

Purpose

Hesperidin (HES) has myriad biological activities that may expedite the wound healing rate. However, the poor aqueous solubility, stability, and bioavailability of HES limit its application. Therefore, a formulation that can address these issues and facilitate its sustained release at the wounded site may be beneficial. In this work, a sesame seed oil-enriched nanostructured lipid carrier hydrogel of HES was prepared and evaluated for its wound healing potential.

Methods

HES-loaded nanostructured lipid carrier (HES-NLCs) were prepared using the hot-homogenization and ultrasonication method. Box-Behnken Design and numerical optimization approach were employed to obtain the optimal formulation. Subsequently, the optimized HES-NLC (OHES-NLC) was loaded into a hydrogel (OHES-NLCG) and characterized. In addition, OHES-NLCG was assessed for the in-vitro drug release, anti-oxidant (DPPH assay), in-vivo wound contraction (full-thickness excisional wound model in rats), and skin irritation (Draize’s primary skin irritation model) potential.

Results

The OHES-NLC with an overall desirability value of 0.90 showed particles in the nanosize range (198.7 nm), narrow distribution (PDI = 0.26), high stability (zeta potential = -29.11 mV), and reasonable percent drug entrapment efficiency (65.23%). Furthermore, OHES-NLCG showed good skin compatibility, and significantly higher (p < 0.05) in-vitro drug permeation (85.80 ± 6.20% vs. 35.61 ± 5.59%) for HES compared to HES-loaded conventional gel (HES-CG). The HES release from the OHES-NLCG followed the Higuchi model (R2 = 0.9869). Moreover, the % DPPH scavenging for OHES-NLCG was significantly higher (p < 0.05) vis-à-vis HES-CG (IC50 value of 34.25 ± 1.3 vs. 67.83 ± 3.2 µg / mL). In addition, OHES-NLCG-treated Wistar rats showed a 94.03 ± 3.28% wound area closure compared to 47.35 ± 4.56% for the untreated rats after 14 days of the wound induction (p < 0.05).

Conclusion

Hence, the outcomes of the study revealed that OHES-NLCG has a promising wound-healing activity in a full-thickness excisional wound model in rats, warranting further detailed investigations.

Graphical Abstract