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Background <p>Diabetic foot ulcers (DFUs) affect 15–25% of diabetic patients due to hyperglycemia-induced inflammation, oxidative stress, microbial infection, and impaired angiogenesis. Curcumin and glycitin, lipophilic polyphenols with synergistic anti-inflammatory, antimicrobial, antioxidant, and wound healing properties, exhibit poor aqueous solubility and stability that limit topical efficacy. Avocado oil nanoemulsion hydrogels offer sustained dual-active delivery for DFU therapy.</p> Purpose <p>This study developed and optimized Tween 80-stabilized curcumin-glycitin avocado oil nanoemulgels using ternary phase diagrams to enhance topical DFU treatment.</p> Methods <p>Nanoemulsions (avocado oil: Tween 80:glycerol) were prepared by high-shear emulsification, optimized via ternary phase diagrams, and incorporated into Carbopol 934/940 hydrogels. Formulations were characterized for droplet size (113–118&#xa0;nm), PDI (&lt; 0.16), zeta potential (-31.8 mV), entrapment efficiency, pH, rheology, UV calibration (curcumin 425&#xa0;nm, r²=0.9992; glycitin 260&#xa0;nm, r²=0.9995), in vitro release (simulated diabetic wound fluid), ex vivo permeation (glucose-pretreated goat skin), FTIR compatibility, antimicrobial activity (<i>Staphylococcus aureus</i>, <i>Pseudomonas aeruginosa</i>), and anti-biofilm efficacy.</p> Results <p>Optimized nanoemulgels demonstrated droplet sizes of 113–118&#xa0;nm (PDI 0.095–0.157), entrapment efficiency &gt; 88% for both actives, sustained release (85% at 24&#xa0;h, Higuchi kinetics), and 3.2-fold enhanced skin permeation versus plain gel (<i>p</i> &lt; 0.05). Validated UV methods showed LODs of 0.32&#xa0;µg/mL (curcumin) and 0.12&#xa0;µg/mL (glycitin). Formulations produced superior zones of inhibition versus controls and &gt; 95% inhibition of <i>S. aureus</i> and <i>P. aeruginosa</i> biofilms.</p> Conclusion <p>Tween 80-stabilized curcumin-glycitin avocado oil nanoemulgels exhibited optimal nanoscale properties, molecular compatibility, controlled release, enhanced diabetic skin permeation, and potent antimicrobial/anti-biofilm activity, establishing their potential as advanced dual-active therapeutics for DFU management.</p> Graphical Abstract <p></p>

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Ternary Phase Diagram-Driven Optimization of a Dual-Active Nanoemulgel for Diabetic Wound Healing: In Vivo Efficacy and Role of Avocado Oil Nanophase on Permeation and Bioactivity of Curcumin and Glycitin

  • 期刊论文

  • 发表日期：

    2026年5月7日

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  • Mahesh Vaggu,
  • Nagashubha Bobbarjang,
  • Haranath Chinthaginjala,
  • Kiran Sai Maccha,
  • Pragathi P.,
  • Shaik Nazifa Mehak,
  • P. Uzma Firdose

摘要

Background

Diabetic foot ulcers (DFUs) affect 15–25% of diabetic patients due to hyperglycemia-induced inflammation, oxidative stress, microbial infection, and impaired angiogenesis. Curcumin and glycitin, lipophilic polyphenols with synergistic anti-inflammatory, antimicrobial, antioxidant, and wound healing properties, exhibit poor aqueous solubility and stability that limit topical efficacy. Avocado oil nanoemulsion hydrogels offer sustained dual-active delivery for DFU therapy.

Purpose

This study developed and optimized Tween 80-stabilized curcumin-glycitin avocado oil nanoemulgels using ternary phase diagrams to enhance topical DFU treatment.

Methods

Nanoemulsions (avocado oil: Tween 80:glycerol) were prepared by high-shear emulsification, optimized via ternary phase diagrams, and incorporated into Carbopol 934/940 hydrogels. Formulations were characterized for droplet size (113–118 nm), PDI (< 0.16), zeta potential (-31.8 mV), entrapment efficiency, pH, rheology, UV calibration (curcumin 425 nm, r²=0.9992; glycitin 260 nm, r²=0.9995), in vitro release (simulated diabetic wound fluid), ex vivo permeation (glucose-pretreated goat skin), FTIR compatibility, antimicrobial activity (Staphylococcus aureus, Pseudomonas aeruginosa), and anti-biofilm efficacy.

Results

Optimized nanoemulgels demonstrated droplet sizes of 113–118 nm (PDI 0.095–0.157), entrapment efficiency > 88% for both actives, sustained release (85% at 24 h, Higuchi kinetics), and 3.2-fold enhanced skin permeation versus plain gel (p < 0.05). Validated UV methods showed LODs of 0.32 µg/mL (curcumin) and 0.12 µg/mL (glycitin). Formulations produced superior zones of inhibition versus controls and > 95% inhibition of S. aureus and P. aeruginosa biofilms.

Conclusion

Tween 80-stabilized curcumin-glycitin avocado oil nanoemulgels exhibited optimal nanoscale properties, molecular compatibility, controlled release, enhanced diabetic skin permeation, and potent antimicrobial/anti-biofilm activity, establishing their potential as advanced dual-active therapeutics for DFU management.

Graphical Abstract