Atorvastatin-loaded nanostructured lipid carriers (NLCs): strategy to overcome oral delivery drawbacks

Figures & data

Table 1. Composition of atorvastatin-loaded nanostructured lipid carriers.

	AT-NLCs composition^a		Physicochemical properties
Run	Solid lipid (2%, w/w)	Aqueous surfactant (2%, w/w)	Mean particle size ± SD (nm)	Zeta potential ± SD (mV)	Entrapment efficiency ± SD (%)	Polydispersity index (PDI)
NLC-1	Gelucire^® 43/01	Pluronic^® F68	162.5 ± 12	−34 ± 0.29	90.1 ± 6.5	0.295
NLC-2	Gelucire^® 43/01	Tween^® 80	199.14 ± 22	−31 ± 0.50	91.3 ± 5.9	0.434
NLC-3	Gelucire^® 43/01	Pluronic^® F68–Tween^® 80 (1:1)	168.54 ± 14	−31 ± 0.25	87.2 ± 7.5	0.261
NLC-4	GMS	Pluronic^® F68	184.98 ± 21	−29 ± 2.8	95.3 ± 5.1	0.276
NLC-5	GMS	Tween^® 80	234 ± 6.8	−28 ± 2.9	92.2 ± 6.2	0.451
NLC-6	GMS	Pluronic^® F68–Tween^® 80 (1:1)	254.4 ± 32.1	−29 ± 2.25	87 ± 4	0.571
NLC-7	Compritol^® 888 ATO	Pluronic^® F68	865.55 ± 28	−28 ± 0.85	94.6 ± 2.6	0.732
NLC-8	Compritol^® 888 ATO	Tween^® 80	224.7 ± 7.5	−23 ± 0.36	76 ± 12.4	0.62
NLC-9	Compritol^® 888 ATO	Pluronic^® F68–Tween^® 80 (1:1)	449.4 ± 3	−24 ± 0.54	96.6 ± 7.1	0.691

^a Each formulation contains 8%, w/w Capryol^® PGMC and 0.5%, w/w lecithin.

Figure 1. (a) TEM image of optimized NLC-1, (b) DSC thermograms of AT, Gelucire^® 43/01and lyophilized NLC-1, (c) in vitro release profiles of (▪) AT suspension and (♦) NLC-1 in phosphate buffer pH 6.8, and (d) average plasma concentration vs. time profiles following single oral administration of NLC-1(♦), AT suspension (▪) and (▴) commercial product.

Table 2. Stability study of NLC-1.

Storage condition	Mean particle size ± SD (nm)	PDI	Zeta potential ± SD (mV)	Entrapment efficiency ± SD (%)
Fresh	162.5 ± 12	0.295	−34 ± 0.29	90.1 ± 6.5
2–8 °C
1 month	173 ± 4.21	0.298	−32.4 ± 0.82	89.45 ± 1.4
3 months	191 ± 3.67	0.308	−32.4 ± 1.37	88.18 ± 1.3
25 °C
1 month	198.6 ± 4.61	0.341	−28.7 ± 0.65	86.12 ± 0.73
3 months	273.6 ± 6.8	0.393	−22.1 ± 0.79	83.31 ± 0.82

Table 3. Pharmacokinetic data of AT following single oral administration (25 mg/kg) of NLC-1, AT suspension and commercial tablet to rats.

Pharmacokinetic parameters	NLC-1	AT suspension	Lipitor^®
Cmax (μg/ml)	25 ± 1.4^a	9.7 ± 1.5	11.9 ± 1.3
Tmax (hr)	2 ± 0.25^a	1.5 ± 0.15	1.5
AUC0–∞ (μg^ahr/ml)	599 ± 224.3^a	168.1 ± 27	286.3 ± 38.5
AUC0–24 (μg^ahr/ml)	370.9 ± 65^a	101.8 ± 2.7	129.3 ± 3.7
Relative bioavailability		3.56	2.09

Each value expressed as the mean ± SD (n = 3).

^a Significant at p < .05.

Table 4. Effect of NLC-1, ATC suspension and Lipitor^® tablet on serum level of total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein.

Group	TC (mg/dl)	TG(mg/dl)	LDL(mg/dl)	HDL (mg/dl)
I (negative control)	50.8 ± 6.87	73 ± 5.24	12.87 ± 8.64	33.26 ± 6.93
II (positive control)	98.5 ± 2.67	178 ± 9.14	86.8 ± 6.48	29.09 ± 5.98
III (atorvastatin suspension)	59.45 ± 4.34^a	123.73 ± 5.11^a	48.37 ± 6.4^a	31.39 ± 2.95
IV (NLC-1)	45.94 ± 3.76^a	99 ± 4.67^a	23.16 ± 3.97^a	37.84 ± 1.79
V (Lipitor^®)	54.7 ± 6.17^a	115.85 ± 7.49^a	38.63 ± 9.43^a	33.34 ± 4.68

Each value expressed as the mean ± SD (n = 3).

^a Significant at p < .05 as compared to positive control group.

Figure 2. Photomicrographs of the liver sections in male albino rats (H&E) (A) control group, (B,C) group fed fructose/HFD supplements, (D) group treated with AT suspension, (E) group treated with NLC-1 and (F) group treated with commercial product.