A promising and effective platform for delivering hydrophilic depigmenting agents in the treatment of cutaneous hyperpigmentation: kojic acid nanostructured lipid carrier

Figures & data

Table 1. Formulation composition and characteristics of investigated KA-NLC dispersion (% w/w).

Formula	Formulation composition (g)											KA-NLCs dispersion characteristics
	KA (%)	Chol (%)	OA (%)	BW (%)	GMS (%)	SA (%)	PA (%)	T 20 (%)	Sp60 (%)	SP 80 (%)	Water (%)	Size (nm)	PDI	ZP (mv)	EE (%)	DL %
KA-NLC1	0.2	0.1	0.3	0. 8	—	—	—	0.2	0.4	—	98.4	349.6 ± 7.3	0.4 ± 0.0	−16.9 ± 0.7	52.8 ± 0.3	9.2 ± 0.1
KA-NLC2	0.2	0.1	0.3	0. 8	—	—	—	0.2	—	0.4	98.4	343.2 ± 35.3	0.4 ± 0.0	−7.6 ± 1.2	57.6 ± 0.8	10.3 ± 0.9
KA-NLC3	0.2	0.1	0.3	—	0.8	—	—	0.2	0.4	—	98.4	172.9 ± 7.1	0.3 ± 0.1	−39.1 ± 2.7	76.4 ± 0.1	17.6 ± 1.3
KA-NLC4	0.2	0.1	0.3	—	0.8	—	—	0.2	—	0.4	98.4	180.0 ± 4.7	0.3 ± 0.1	−39.2 ± 0.8	62.5 ± 1.4	17.2 ± 1.1
KA-NLC5	0.2	0.1	0.3	—	—	0.8	—	0.2	0.4	—	98.4	255.9 ± 14.6	0.4 ± 0.0	−20.7 ± 1.5	57.1 ± 1.3	15.2 ± 0.5
KA-NLC6	0.2	0.1	0.3	—	—	0.8	—	0.2	—	0.4	98.4	277.8 ± 35.4	0.4 ± 0.0	−6.6 ± 2.0	51.9 ± 2.0	14.1 ± 0.8
KA-NLC7	0.2	0.1	0.3	—	—	—	0.8	0.2	0.4	—	98.4	339.5 ± 53.8	0.4 ± 0.1	−22.6 ± 1.5	55.1 ± 0.1	12.2 ± 1.5
KA-NLC8	0.2	0.1	0.3	—	—	—	0.8	0.2	—	0.4	98.4	365.5 ± 22.1	0.4 ± 0.0	−8.7 ± 1.2	59.5 ± 1.3	13.2 ± 0.9

Data are expressed as mean ± SD.

KA: kojic acid; Chol: cholesterol; OA: oleic acid; BW: beeswax; GMS; glycerol monostearate; SA: stearic acid; PA: palmitic acid; T 20: tween 20; SP: span60; PDI: polydispersity index; ZP: zeta.

Figure 1. TEM micrographs of KA-NLC₃ dispersion.

Figure 2. The ATR-FTIR spectra of KA, Chol, GMS, OA, physical mixture, and KA-NLC₃ dispersion.

Figure 3. DSC thermograms obtained for KA, Chol, GMS, physical mixtures, and KA-NLC₃ dispersion.

Figure 4. XRD of KA, Chol, GMS, physical mixtures, and KA-NLC₃ dispersion.

Figure 5. Dissolution profile of KA solution and KA-NLC₃ dispersion.

Figure 6. Curves of tyrosinase mushroom activity of KA solution and KA-NLC₃ dispersion. (A) The concentrations of KA were 100, 50, 25, 10, 5 µg/ml and (B) the concentrations of KA-NLC₃ dispersion were 10, 5, 2.5, 2,1, 0.5, and 0.25 µg/ml. IC50 values were calculated by nonlinear regression using Graph Pad Prism 5.0.

Figure 7. Ex vivo and in vitro permeation profiles of KA-NLC₃ dispersion and KA solution across human, rat and synthetic skins. Data are presented as mean and standard deviation of three determinations (n = 3).

Figure 8. Cumulative amount of KA in the membrane layers, including rat skin, HEM and synthetic membrane.

Table 2. Stability information of the KA-NLC₃ dispersion after 3 months of storage.

Formulation	Storage condition	Time	Particle size (nm)	PDI	ZP (mV)	EE%
KA-NLC3 dispersion	Initial	—	172.9 ± 7.1	0.3 ± 0.1	−39.1 ± 2.7	76.4 ± 0.1
	4–8 °C	After 3 months	181.5 ± 1.1	0.5 ± 0.0	−34.1 ± 0.4	60.1 ± 0.0
	At room temperature (RT)		237.5 ± 0.3	0.6 ± 0.8	−25.7 ± 0.2	41.2 ± 0.2

Data are expressed as mean ± SD.

Figure 9. Viability of normal human skin fibroblast cells (HFF-1) (MTT assay) after 24, 48, and 72 h exposure to (a) KA solution for 24, 48, and 72 h, (b) NLC-drug (KA) and NLC + drug (KA) for 24 h, (c) NLC-drug (KA) and NLC + drug (KA) for 48 h, (d) NLC-drug (KA) and NLC + drug (KA) for 72 h. Data represented as the means ± SD of eight identical experiments. ***p<.001 expression in the formulations treated cells versus the untreated cells.