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Background and objectives <p>Wound healing is one of the growing concerns, which, when worsened, can lead to amputation of the limbs and even loss of life. Flavonoids, a potent group of polyphenols, possess significant wound-healing potential due to their antioxidant, anti-inflammatory, antimicrobial, angiogenic-promoting, and diabetes-regulating actions. Naringenin, a citrus flavanone within the broad flavonoid family with the above-mentioned potential, has been selected for targeting wound healing. To deliver naringenin to the specific site, the present study aims to develop a transferosome-encapsulated gel for enhanced wound healing performance compared with control in a rat excision model.</p> Methods <p>In due course, a 3-factor 3-level Box-Behnken design was employed to develop an optimized transferosome for loading naringenin, with phospholipid (%), surfactant (%), and ethanol (%) as independent variables and particle size (nm) and PDI as dependent variables.</p> Results <p>The transferosome was fabricated using the thin-film hydration method, and the optimized formulation has a particle size of 148.30 ± 2.066&#xa0;nm, a PDI of 0.460 ± 0.002, and a Zeta potential of -3.403 ± 0.857 mV. The optimized transferosome was further incorporated into a polymeric matrix composed of Poloxamer 407 and HPMC to obtain a stimuli-responsive transferosome-based gel. The transferosome-infused in situ gel displayed entrapment efficiency of 92.22 ± 0.2% and in vitro drug release of 94.65 ± 0.2%. Furthermore, the optimized transferosomal gel demonstrated in vitro antioxidant, anti-inflammatory, and antimicrobial properties, highlighting its role in wound healing. Thereafter, the safety of the optimized formulation was assessed according to OECD guidelines, which indicated that it was harmless when applied to the skin surface of the experimental animals. Finally, the wound-healing efficacy of the optimized formulation was evaluated in an excision wound model in Sprague-Dawley rats, which indicated a faster wound contraction with 100% wound closure by day 12 (<i>p</i> &lt; 0.05).</p> Conclusion <p>Overall, it can be inferred that the optimized naringenin-encapsulated transferosomal in situ gel could be a viable tool for wound treatment.</p> Graphical abstract <p></p>

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Box-Behnken Design (BBD) Based Development of Naringenin Encapsulated Transferosome Infused In Situ Gel for Wound Healing: Safety Study, Efficacy Assessment and In Vitro Evaluation

  • 期刊论文

  • 发表日期：

    2026年6月30日

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  • Ankit Chowdhury,
  • Bapi Gorain,
  • Papiya Mitra Mazumder

摘要

Background and objectives

Wound healing is one of the growing concerns, which, when worsened, can lead to amputation of the limbs and even loss of life. Flavonoids, a potent group of polyphenols, possess significant wound-healing potential due to their antioxidant, anti-inflammatory, antimicrobial, angiogenic-promoting, and diabetes-regulating actions. Naringenin, a citrus flavanone within the broad flavonoid family with the above-mentioned potential, has been selected for targeting wound healing. To deliver naringenin to the specific site, the present study aims to develop a transferosome-encapsulated gel for enhanced wound healing performance compared with control in a rat excision model.

Methods

In due course, a 3-factor 3-level Box-Behnken design was employed to develop an optimized transferosome for loading naringenin, with phospholipid (%), surfactant (%), and ethanol (%) as independent variables and particle size (nm) and PDI as dependent variables.

Results

The transferosome was fabricated using the thin-film hydration method, and the optimized formulation has a particle size of 148.30 ± 2.066 nm, a PDI of 0.460 ± 0.002, and a Zeta potential of -3.403 ± 0.857 mV. The optimized transferosome was further incorporated into a polymeric matrix composed of Poloxamer 407 and HPMC to obtain a stimuli-responsive transferosome-based gel. The transferosome-infused in situ gel displayed entrapment efficiency of 92.22 ± 0.2% and in vitro drug release of 94.65 ± 0.2%. Furthermore, the optimized transferosomal gel demonstrated in vitro antioxidant, anti-inflammatory, and antimicrobial properties, highlighting its role in wound healing. Thereafter, the safety of the optimized formulation was assessed according to OECD guidelines, which indicated that it was harmless when applied to the skin surface of the experimental animals. Finally, the wound-healing efficacy of the optimized formulation was evaluated in an excision wound model in Sprague-Dawley rats, which indicated a faster wound contraction with 100% wound closure by day 12 (p < 0.05).

Conclusion

Overall, it can be inferred that the optimized naringenin-encapsulated transferosomal in situ gel could be a viable tool for wound treatment.

Graphical abstract