Preparation, characterization and pharmacokinetic studies of linalool-loaded nanostructured lipid carriers

Figures & data

Figure 1. Chemical Structure of linalool.

Table 1. Central composite design (CCD) matrix of four independent variables and the experimental results.

	Coded values				Actual values				Response values
					GMS	MCT	S80	T80	Particle size
Trial	X1	X2	X3	X4	(%)	(%)	(%)	(%)	nm
1	–1	1	–1	–1	2.5	5.5	2	2	84.75
2	–1	–1	1	–1	2.5	2.5	4	2	97.67
3	–1	–1	1	1	2.5	2.5	4	4	62.88
4	0	0	0	0	4	4	3	3	73.37
5	1	1	1	1	5.5	5.5	4	4	77.54
6	1	1	1	–1	5.5	5.5	4	2	116.7
7	0	0	0	0	4	4	3	3	79.54
8	0	0	0	2	4	4	3	5	75.48
9	0	2	0	0	4	7	3	3	73.17
10	1	1	–1	1	5.5	5.5	2	4	69.28
11	0	0	0	0	4	4	3	3	77.89
12	2	0	0	0	7	4	3	3	98.04
13	0	0	0	0	4	4	3	3	73.53
14	1	–1	1	–1	5.5	2.5	4	2	111
15	–1	1	–1	1	2.5	5.5	2	4	52.97
16	–2	0	0	0	1	4	3	3	61.78
17	–1	1	1	–1	2.5	5.5	4	2	94.27
18	–1	–1	–1	1	2.5	2.5	2	4	43.84
19	–1	–1	–1	–1	2.5	2.5	2	2	73.68
20	0	0	0	0	4	4	3	3	73.89
21	0	–2	0	0	4	1	3	3	79.74
22	1	–1	–1	1	5.5	2.5	2	4	63.55
23	0	0	–2	0	4	4	1	3	65.08
24	1	–1	1	1	5.5	2.5	4	4	70.77
25	1	1	–1	–1	5.5	5.5	2	2	112.5
26	0	0	2	0	4	4	5	3	83.79
27	0	0	0	–2	4	4	3	1	135.6
28	–1	1	1	1	2.5	5.5	4	4	66.97
29	0	0	0	0	4	4	3	3	78.25
30	1	–1	–1	–1	5.5	2.5	2	2	102.8

Table 2. ANOVA of the response surface model with 95% confidence level.

Source	Sum of squares	DF	Mean square	F value	p Value
Model	11 309.485	14	807.8203604	42.6983001	<0.0001^a
X1	2009.88904	1	2009.889038	106.235061	<0.0001^a
X2	52.9551042	1	52.95510417	2.79900463	0.115
X3	724.350938	1	724.3509375	38.2864251	<0.0001^a
X4	6861.73984	1	6861.739838	362.685371	<0.0001^a
X1X2	3.07125625	1	3.07125625	0.16233488	0.6927
X1X3	93.4605562	1	93.46055625	4.93996819	0.0420^a
X1X4	90.9639062	1	90.96390625	4.8080048	0.0445^a
X2X3	31.5563062	1	31.55630625	1.66794587	0.2161
X2X4	0.43890625	1	0.43890625	0.02319891	0.881
X3X4	0.42575625	1	0.42575625	0.02250385	0.8828
X1^2	6.79158601	1	6.791586012	0.35897731	0.558
X2^2	3.6771503	1	3.677150298	0.19436013	0.6656
X3^2	20.8154074	1	20.81540744	1.10022297	0.3108
X4^2	1307.807	1	1307.807	69.1256851	<0.0001^a
Residual	283.788942	15	18.91926278	–	–
Lack of fit	245.189658	10	24.51896583	3.17609081	0.107
Pure error	38.5992833	5	7.719856667	–	–
Corrected total	11 593.274	29	–	–	–

The symbol of ^‘a’ means the term is significant. R² =0.976, CV = 5.37%.

Figure 2. Three-dimensional (3D) response surfaces of two interaction effects on particle size (PS).

Figure 3. Particle size distribution of LL-NLCs.

Figure 4. Zeta potential distribution of LL-NLCs.

Figure 5. Transmission electron microscope (TEM) image of LL-NLCs.

Figure 6. X-ray diffraction (XRD) images of mannitol, sucrose, glycerin monostearate (GMS), LL-NLCs and physical mixture of LL-NLCs/20% mannitol/20% sucrose.

Figure 7. Differential scanning calorimetry (DSC) thermograms of mannitol, sucrose, GMS, LL-NLCs and physical mixture of LL-NLCs/20% mannitol/20% sucrose.

Figure 8. Dissolution curves of LL from free LL and LL-NLCs.

Figure 9. Time-dependent changes of LL-NLCs in the stability test (25 °C).

Figure 10. Drug concentration-time curve in plasma of LL after intragastric administration (n = 6).

Table 3. Pharmacokinetic parameters of LL after intragastric administration in rats (mean, n = 6).

	t1/2	MRT	Cmax	tmax	AUC0–t	Fr
Parameter	(min)	(min)	(ng × mL^−1)	(min)	(ng × min × mL^−1)	(%)
Free LL	44.72	45.66	1915.45	40	76003.40	–
LL-NLCs	110.50	146.66	2182.45	60	298948.46	393.34