Topical application of omega-3-, omega-6-, and omega-9-rich oil emulsions for cutaneous wound healing in rats

Drug Deliv Transl Res. 2019 Apr;9(2):418-433. doi: 10.1007/s13346-018-0522-8.


Wound healing is a physiological event that generates reconstitution and restoration of granulation tissue that ends with scar formation. As omega fatty acids are part of membrane phospholipids and participate in the inflammatory response, we investigated the effects of omega-3, omega-6, and omega-9 fatty acids in the form of oils on wound healing. Linseed (LO), evening primrose (EPO), and olive oils (OO) rich in omega-3, omega-6, and omega-9 fatty acids were formulated into emulsions and were topically applied on rats with excision wounds. All omega-3-, omega-6-, and omega-9-rich oil formulations were found to accelerate wound closure compared to untreated, with significant improvement (p < 0.05) being observed at day 14. EPO induced early deposition of collagen as evaluated by Masson trichrome staining that correlated well with the hydroxyproline content assay, with the highest level at days 3 and 7. Vascular endothelial growth factor (VEGF) showed greater amount of new microvasculature formed in the EPO-treated group, while moderate improvement occurs in the LO and OO groups. EPO increased both the expression of proinflammatory cytokines and growth factors in the early stage of healing and declined at the later stage of healing. LO modulates the proinflammatory cytokines and chemokine but did not affect the growth factors. In contrast, OO induced the expression of growth factors rather than proinflammatory cytokines. These data suggest that LO, EPO, and OO emulsions promote wound healing but they accomplish this by different mechanisms.

Keywords: Cytokines; Emulsion; Hydroxyproline; Omega oil; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Collagen / metabolism
  • Emulsions
  • Fatty Acids / administration & dosage*
  • Female
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • Oils / administration & dosage*
  • Rats, Wistar
  • Skin / drug effects*
  • Skin / injuries
  • Skin / metabolism
  • Skin / pathology
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects*


  • Emulsions
  • Fatty Acids
  • Intercellular Signaling Peptides and Proteins
  • Oils
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Collagen