Hydrogel composite containing azelaic acid and tea tree essential oil as a therapeutic strategy for Propionibacterium and testosterone-induced acne

Drug Deliv Transl Res. 2022 Oct;12(10):2501-2517. doi: 10.1007/s13346-021-01092-4. Epub 2021 Nov 15.


Azelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index < 0.7), nano-range (~357.4 ± 2% nm), transmittance (> 90%), and negative zeta potential (-1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris.

Keywords: Agar well diffusion method; Broth microdilution assay; P. acne; Rheology; Skin permeation, Testosterone acne model.

MeSH terms

  • Acne Vulgaris* / chemically induced
  • Acne Vulgaris* / drug therapy
  • Acne Vulgaris* / microbiology
  • Animals
  • Dicarboxylic Acids
  • Hydrogels / therapeutic use
  • Propionibacterium
  • Rats
  • Rats, Wistar
  • Tea
  • Tea Tree Oil*
  • Testosterone / therapeutic use
  • Trees


  • Dicarboxylic Acids
  • Hydrogels
  • Tea
  • Testosterone
  • Tea Tree Oil
  • azelaic acid