Development of a kojic monooleate-enriched oil-in-water nanoemulsion as a potential carrier for hyperpigmentation treatment
Received 18 April 2018
Accepted for publication 21 June 2018
Published 15 October 2018 Volume 2018:13 Pages 6465—6479
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Thomas Webster
Sharifah Nurfadhlin Afifah Syed Azhar, Siti Efliza Ashari, Norazlinaliza Salim
Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
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: kojic monooleate, anti-tyrosinase, hyperpigmentation, nano-cosmeceutical, D-optimal mixture experimental design
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