Spray-by-spray in situ cross-linking alginate hydrogels delivering a tea tree oil microemulsion

Eur J Pharm Sci. 2015 Jan 23:66:20-8. doi: 10.1016/j.ejps.2014.09.018. Epub 2014 Sep 30.


In this paper we propose an in situ forming ionically cross-linked alginate (Alg) hydrogel delivering a Tea Tree Oil microemulsion (MeTTO) and potentially useful as an advanced dressing for infected wounds. Alg hydrogels were prepared by a spray-by-spray deposition method with the aim to minimize the discomforts during application. From pseudoternary phase diagrams, it was found that proper combination of TTO, water, polysorbate 80 and ethanol gave stable spherical MeTTO with good antimicrobial activity. On this basis, MeTTO at 20% TTO was selected for further inclusion in an Alg hydrogel prepared by alternating sprays of Alg/MeTTO and calcium chloride solutions. Homogeneous dispersion of MeTTO inside cross-linked Alg was assessed by different macroscopic and microscopic methods demonstrating the superior propensity of MeTTO to be integrated in the water-based hydrogel as compared to TTO. Antimicrobial effect of Alg/MeTTO hydrogels on Escherichia Coli strains was remarkable, highlighting the potential of the system as bioactive wound dressing.

Keywords: Advanced dressing; Alginate; Microemulsions; Spray-by-spray; Tea tree oil.

MeSH terms

  • Aerosols
  • Alginates / chemistry*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Emulsions / chemistry*
  • Escherichia coli / drug effects
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Hydrogels / chemistry*
  • Microbial Sensitivity Tests
  • Microscopy, Electron, Scanning / methods
  • Polysorbates
  • Tea Tree Oil / chemistry*


  • Aerosols
  • Alginates
  • Anti-Bacterial Agents
  • Emulsions
  • Hexuronic Acids
  • Hydrogels
  • Polysorbates
  • Tea Tree Oil
  • Glucuronic Acid