Development of a kojic monooleate-enriched oil-in-water nanoemulsion as a potential carrier for hyperpigmentation treatment

Int J Nanomedicine. 2018 Oct 15;13:6465-6479. doi: 10.2147/IJN.S171532. eCollection 2018.

Abstract

Introduction: Kojic monooleate (KMO) is an ester derived from a fungal metabolite of kojic acid with monounsaturated fatty acid, oleic acid, which contains tyrosinase inhibitor to treat skin disorders such as hyperpigmentation. In this study, KMO was formulated in an oil-in-water nanoemulsion as a carrier for better penetration into the skin.

Methods: The nanoemulsion was prepared by using high and low energy emulsification technique. D-optimal mixture experimental design was generated as a tool for optimizing the composition of nanoemulsions suitable for topical delivery systems. Effects of formulation variables including KMO (2.0%-10.0% w/w), mixture of castor oil (CO):lemon essential oil (LO; 9:1) (1.0%-5.0% w/w), Tween 80 (1.0%-4.0% w/w), xanthan gum (0.5%-1.5% w/w), and deionized water (78.8%-94.8% w/w), on droplet size as a response were determined.

Results: Analysis of variance showed that the fitness of the quadratic polynomial fits the experimental data with F-value (2,479.87), a low P-value (P<0.0001), and a nonsignificant lack of fit. The optimized formulation of KMO-enriched nanoemulsion with desirable criteria was KMO (10.0% w/w), Tween 80 (3.19% w/w), CO:LO (3.74% w/w), xanthan gum (0.70% w/w), and deionized water (81.68% w/w). This optimum formulation showed good agreement between the actual droplet size (110.01 nm) and the predicted droplet size (111.73 nm) with a residual standard error <2.0%. The optimized formulation with pH values (6.28) showed high conductivity (1,492.00 µScm-1) and remained stable under accelerated stability study during storage at 4°C, 25°C, and 45°C for 90 days, centrifugal force as well as freeze-thaw cycles. Rheology measurement justified that the optimized formulation was more elastic (shear thinning and pseudo-plastic properties) rather than demonstrating viscous characteristics. In vitro cytotoxicity of the optimized KMO formulation and KMO oil showed that IC50 (50% inhibition of cell viability) value was >100 µg/mL.

Conclusion: The survival rate of 3T3 cell on KMO formulation (54.76%) was found to be higher compared to KMO oil (53.37%) without any toxicity sign. This proved that the KMO formulation was less toxic and can be applied for cosmeceutical applications.

Keywords: D-optimal mixture experimental design; anti-tyrosinase; hyperpigmentation; kojic monooleate; nano-cosmeceutical.

MeSH terms

  • 3T3 Cells
  • Analysis of Variance
  • Animals
  • Cell Death / drug effects
  • Emulsions / chemistry*
  • Hyperpigmentation / drug therapy*
  • Mice
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure*
  • Oils / chemistry*
  • Oleic Acid / therapeutic use*
  • Particle Size
  • Pyrones / therapeutic use*
  • Pyrones / toxicity
  • Reproducibility of Results
  • Solubility
  • Time Factors
  • Water / chemistry*

Substances

  • Emulsions
  • Oils
  • Pyrones
  • Water
  • Oleic Acid
  • kojic acid