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<p>Topical drug delivery offers significant advantages in wound management by enabling direct therapeutic action at the site of injury while minimizing systemic drug exposure. Indomethacin (IM), a potent nonsteroidal anti-inflammatory drug (NSAID), plays a vital role in the wound healing process by effectively controlling inflammation. This research aimed to develop an Indomethacin-loaded nanoemulsion hydrogel (NEG-IM) to enhance drug penetration through the skin, improve wound healing performance, and ensure that the drug remains within the formulation. When tested with a ternary phase diagram, the nanoemulsion composition reached optimal stability, which yielded droplets smaller than 200&#xa0;nm and achieved entrapment efficiencies from 83 to 88%. The optimized nanoemulsion contained Sodium Stearate at ratios of 25–50%, Avocado Oil at 50–75%, and Glycerol at ratios of 25–50%. This combination optimized emulsification and promoted gel texture formation while decreasing drug leakage. The drug release evaluation using DR showed 89.78%, while PC measurement through permeation coefficient reached 0.507&#xa0;cm<sup>2</sup>/h, demonstrating effective transdermal delivery. The antibacterial capabilities of NEG-IM surpassed pure IM and conventional IM gels through its minimum bactericidal concentrations, which reached 259&#xa0;µg/mL for E. coli, 132&#xa0;µg/mL for S. aureus, and 527&#xa0;µg/mL for P. aeruginosa. Cell viability tests demonstrated that the cells maintained their viability at more than 85% level throughout the concentration range of up to 8&#xa0;µg/mL (86% at 2&#xa0;µg/mL, 89% at 4&#xa0;µg/mL, and 87% at 8&#xa0;µg/mL) while showing a concentration-dependent decrease at higher levels. The fluorescence intensity measurements of IM-loaded nanoemulsion during cellular uptake remained steady at 742 at 2&#xa0;h, then decreased to 698 at 4&#xa0;h and 695 at 6&#xa0;h, indicating stable internalization. However, NEG-IM demonstrated a slow rise in uptake over 6&#xa0;h from 212 to 536 in fluorescence intensity results.</p>

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Ternary phase optimized indomethacin nanoemulsion hydrogel for sustained topical delivery and improved biological efficacy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月8日

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  • K. R. Nithin,
  • G. M. Pallavi,
  • K. S. Srikruthi,
  • Kasim Sakran Abass,
  • Nimbagal Raghavendra Naveen

摘要

Topical drug delivery offers significant advantages in wound management by enabling direct therapeutic action at the site of injury while minimizing systemic drug exposure. Indomethacin (IM), a potent nonsteroidal anti-inflammatory drug (NSAID), plays a vital role in the wound healing process by effectively controlling inflammation. This research aimed to develop an Indomethacin-loaded nanoemulsion hydrogel (NEG-IM) to enhance drug penetration through the skin, improve wound healing performance, and ensure that the drug remains within the formulation. When tested with a ternary phase diagram, the nanoemulsion composition reached optimal stability, which yielded droplets smaller than 200 nm and achieved entrapment efficiencies from 83 to 88%. The optimized nanoemulsion contained Sodium Stearate at ratios of 25–50%, Avocado Oil at 50–75%, and Glycerol at ratios of 25–50%. This combination optimized emulsification and promoted gel texture formation while decreasing drug leakage. The drug release evaluation using DR showed 89.78%, while PC measurement through permeation coefficient reached 0.507 cm2/h, demonstrating effective transdermal delivery. The antibacterial capabilities of NEG-IM surpassed pure IM and conventional IM gels through its minimum bactericidal concentrations, which reached 259 µg/mL for E. coli, 132 µg/mL for S. aureus, and 527 µg/mL for P. aeruginosa. Cell viability tests demonstrated that the cells maintained their viability at more than 85% level throughout the concentration range of up to 8 µg/mL (86% at 2 µg/mL, 89% at 4 µg/mL, and 87% at 8 µg/mL) while showing a concentration-dependent decrease at higher levels. The fluorescence intensity measurements of IM-loaded nanoemulsion during cellular uptake remained steady at 742 at 2 h, then decreased to 698 at 4 h and 695 at 6 h, indicating stable internalization. However, NEG-IM demonstrated a slow rise in uptake over 6 h from 212 to 536 in fluorescence intensity results.