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Purpose <p><i>Dalbergia sissoo</i> and <i>Curcuma longa</i> possess established anti-inflammatory and wound-healing properties; however, their key phytoconstituents exhibit poor aqueous solubility and limited membrane permeability, restricting transdermal efficacy. This study aimed to develop and evaluate transdermal ethosomal gels (TEGs) of these extracts to enhance skin penetration, wound repair, and anti-inflammatory activity using a Quality by Design (QbD) approach.</p> Methods <p>Ethosomal formulations of powdered extracts of <i>D. sissoo</i> (PEDS) and <i>C. longa</i> (PECL) were optimized via Box–Behnken Design for particle size and entrapment efficiency. The optimized formulation (F6) was incorporated into three TEGs (G1–G3; pH 7.4, 7.0, and 5.5) and compared with a non-ethosomal gel (NG). Physicochemical characterization, in vitro release (Franz diffusion cell), in vivo wound healing (excision model), and anti-inflammatory activity (carrageenan-induced paw edema) were performed. Molecular docking assessed phytoconstituent interactions with hTNF-α.</p> Results <p>F6 displayed small vesicle sizes (PEDS: 110 ± 4.78&#xa0;nm; PECL: 100 ± 3.05&#xa0;nm; PDI &lt; 0.15), high entrapment efficiency (~ 98%), and stable zeta potential (− 50.2 mV). G3 (pH 5.5) showed the highest drug release (PEDS: 96.14%; PECL: 98.64% at 6&#xa0;h). In vivo, TG3 achieved 98.47 ± 0.82% wound closure by day 8, complete closure by day 12, and the shortest epithelization period (7 days), significantly outperforming NG (<i>p</i> &lt; 0.01). TG3 also exhibited the highest anti-inflammatory effect (69.3% inhibition at 360&#xa0;min, <i>p</i> &lt; 0.01 vs. NG). Docking studies confirmed strong hTNF-α binding by dalbergin and curcuminoids, correlating with observed biological activity.</p> Conclusion <p>G3 (pH 5.5 TEG) significantly enhances transdermal delivery, wound healing, and anti-inflammatory effects, underscoring its potential as therapeutic candidate for inflammatory skin conditions.</p> Graphical Abstract <p></p>

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Innovative Transdermal Delivery of Synergistic Phytoconstituents from Dalbergia Sissoo and Curcuma Longa: Formulation, Characterization, and Biological Efficacy

  • 期刊论文

  • 发表日期：

    2025年10月1日

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  • Vishnu Das,
  • Joohee Pradhan

摘要

Purpose

Dalbergia sissoo and Curcuma longa possess established anti-inflammatory and wound-healing properties; however, their key phytoconstituents exhibit poor aqueous solubility and limited membrane permeability, restricting transdermal efficacy. This study aimed to develop and evaluate transdermal ethosomal gels (TEGs) of these extracts to enhance skin penetration, wound repair, and anti-inflammatory activity using a Quality by Design (QbD) approach.

Methods

Ethosomal formulations of powdered extracts of D. sissoo (PEDS) and C. longa (PECL) were optimized via Box–Behnken Design for particle size and entrapment efficiency. The optimized formulation (F6) was incorporated into three TEGs (G1–G3; pH 7.4, 7.0, and 5.5) and compared with a non-ethosomal gel (NG). Physicochemical characterization, in vitro release (Franz diffusion cell), in vivo wound healing (excision model), and anti-inflammatory activity (carrageenan-induced paw edema) were performed. Molecular docking assessed phytoconstituent interactions with hTNF-α.

Results

F6 displayed small vesicle sizes (PEDS: 110 ± 4.78 nm; PECL: 100 ± 3.05 nm; PDI < 0.15), high entrapment efficiency (~ 98%), and stable zeta potential (− 50.2 mV). G3 (pH 5.5) showed the highest drug release (PEDS: 96.14%; PECL: 98.64% at 6 h). In vivo, TG3 achieved 98.47 ± 0.82% wound closure by day 8, complete closure by day 12, and the shortest epithelization period (7 days), significantly outperforming NG (p < 0.01). TG3 also exhibited the highest anti-inflammatory effect (69.3% inhibition at 360 min, p < 0.01 vs. NG). Docking studies confirmed strong hTNF-α binding by dalbergin and curcuminoids, correlating with observed biological activity.

Conclusion

G3 (pH 5.5 TEG) significantly enhances transdermal delivery, wound healing, and anti-inflammatory effects, underscoring its potential as therapeutic candidate for inflammatory skin conditions.

Graphical Abstract