Optimization and characterization of curcumin loaded coconut oil–honey nanoemulsion for skin permeability enhancement

Abstract

Nanoemulsion which consists of particles in a nanometer range is one of the common carriers for dermal and transdermal drug delivery. This delivery system is suitable for encapsulates active compounds that are poorly soluble in water. Curcumin is a lipohilic bioactive compound with poor bioavailability, and therefore, nanoencapsulation was used to increase its stability and skin permeability. This study focused on the optimization and characterization of curcumin nanoemulsion composed of coconut oil, Tween 80 (surfactant) and polyethylene glycol (co–solvent), with honey and glycerol as additives. The formulation of nanoemulsion was optimized and systematically characterized for transdermal delivery. Response surface methodology (RSM) with Box Behnken design was used to optimize the base formulation based on the three independent variables that were honey (1–3 %), virgin coconut oil (1.0–1.5 %) and Tween 80 (5.0–9.0 %) which led to formation of formulation with low particle size 10.11 nm, polydispersity index 0.27 and turbidity 0.24–1.11 system. Subsequently, the optimization of curcumin nanoemulsion was carried out again after curcumin was loaded into the base formulation. Another three independent variables that were polyethelene glycol (0.8–1.5 %), curcumin (0.01–0.1 %) and honey (1.8–2.4 %) were used to produce the nano–range of particle size 14.32 nm, narrow polydispersity index 0.152, and high encapsulation efficiency 98.0 %. Slight acidic (pH 4.18) curcumin nanoemulsion was obtained without any chemical degradation based on the results of attenuated total reflection – Fourier transform infrared (ATR– FTIR). The incorporation of curcumin inside nanoglobuls improved curcumin stability and skin permeability. The curcumin loaded nanoemulsion was found to have high stability with only 8.5 % increment in particle size after it was stored for 3 months at 4 °C and 45 °C. The radical scavenging activity of encapsulated curcumin in nanoemulsion was slightly decreased (7.9 %) compared to free curcumin. Nanoemulsion appeared to increase the in vitro release rate of curcumin for about 42.3 %, especially for the first 2 hours in Franz diffusion cell using rat skin. Its high permeability can be seen from Nile dyed curcumin in different layers of skin through fluorescent imaging. The release kinetic of curcumin nanoemulsion followed the Higuchi model which explains a Fickian diffusion controlled skin permeation because the Korsmeyer constant was proven to be 0.3 (< 0.5). Curcumin nanoemulsion showed low cytotoxicity (EC50 2.3652 µg/mL) to human skin fibroblasts. Cell death was noticed at high concentration (2.5000 µg/mL) of treatment. Curcumin was also found to promote wound closure at low concentration of 0.1563 µg/mL and its performance is comparable with the performance of ascorbic acid based on scratch assay. Therefore, this nutritious curcumin nanoemulsion is a promising transdermal delivery system for topical application.