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

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.