Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery

Figures & data

Table 1 Characterization of self-nanoemulsifying drug delivery systems in double-distilled water and simulated gastric fluid by mean diameter, zeta potential, and particle numbers

Characteristics	Double-distilled water	Simulated gastric fluid
Size (nm)	173.5±1.0	190.0±2.5
Polydispersity index	0.39±0.004	0.42±0.04
Zeta potential (mV)	−18.9±0.3	−0.6±0.3
Droplet number (droplets/mL)	1.3×10^11	1.0×10^11

Note: Each value represents the mean ± standard deviation (n=3).

Figure 1 Transmission electron micrographs of self-nanoemulsifying drug delivery systems at magnifications of (A) 75,000× and (B) 200,000×. The scale bar is 100 nm.

Figure 2 RYGB in the rat model.

Notes: (A) Intraoperative imaging of RYGB rat. (B) View of gastrointestinal tract exposed outside the abdominal cavity. The arrow indicates the connection of the gastric pouch to the Roux limb. The triangle indicates the connection of the biliopancreatic limb and the Roux limb. (C) Change in body weight of sham rats and RYGB rats after surgery.

Abbreviations: R, remaining stomach; GP, gastric pouch; BP limb, biliopancreatic limb; RYGB, Roux-en-Y gastric bypass.

Table 2 Pharmacokinetic parameters of silibinin (144 mg/kg) after oral administration of silymarin from suspension, PEG 400 solution, and SNEDDS in control rats

Parameter	Suspension	PEG 400	SNEDDS
Cmax (μg/mL)	7.54±0.79	12.94±6.57	11.84±6.21
Tmax (hours)	1.33±0.29	1.67±1.21	1.31±0.65
AUC (μg·hour/mL)	99.97±7.73	179.55±44.21	163.42±48.05
Half-life (hours)	15.03±1.42	10.45±2.25	9.04±3.37
Clearance (mL/hour/kg)	823.01±86.64	801.99±230.03	881.15±222.49
MRT (hours)	24.16±2.42	15.66±5.46	12.68±5.17

Note: Each value represents the mean ± standard deviation (n=5–10).

Abbreviations: C_max, maximum plasma concentration; T_max, time to reach C_max; AUC, area under the plasma concentration-time curve; MRT, mean residence time; PEG, polyethylene glycol; SNEDDS, self-nanoemulsifying drug delivery systems.

Figure 3 Pharmacokinetic profiles of silibinin after oral administration of aqueous suspension, PEG 400 solution, and SNEDDS.

Notes: (A) Mean plasma concentration of silibinin versus time curves in normal rats. (B) Mean plasma concentration of silibinin versus time curves in RYGB rats. (C) Comparison of area under curve (AUC) of the plasma concentration-time curves. *P<0.05, **P<0.01.

Abbreviations: RYGB, Roux-en-Y gastric bypass; PEG, polyethylene glycol; SNEDDS, self-nanoemulsifying drug delivery systems.

Table 3 Pharmacokinetic parameters of silibinin (144 mg/kg) after oral administration of silymarin from suspension, PEG 400 solution, and SNEDDS in RYGB rats

Parameter	Suspension	PEG 400	SNEDDS
Cmax (μg/mL)	5.37±4.72	13.77±6.72	13.65±5.59
Tmax (hours)	4.71±2.50	2.0±0	2.83±1.29
AUC (μg·hour/mL)	72.77±27.18	123.20±22.44	180.15±40.86
Half-life (hours)	8.46±3.86	6.39±1.75	8.45±2.22
Clearance (mL/hour/kg)	1,978.91±606.38	1,168.78±394.34	986.06±255.57
MRT (hours)	12.46±4.48	9.91±3.71	11.26±3.90

Note: Each value represents the mean ± standard deviation (n=5–10).

Abbreviations: C_max, maximum plasma concentration; T_max, time to reach C_max; AUC, area under the plasma concentration-time curve; MRT, mean residence time; RYGB, Roux-en-Y gastric bypass; PEG, polyethylene glycol; SNEDDS, self-nanoemulsifying drug delivery systems.

Figure 4 Fluorescence imaging of stomach and intestine of rats after oral administration of Nile red-containing PEG 400 solution and SNEDDS.

Notes: (A) Macroscopic observation of GI tract exposed outside the abdominal cavity after oral administration of PEG 400 and SNEDDS in RYGB rats. The arrows indicate the connection of gastric pouch to the Roux limb. (B) Microscopic observation of stomach (100×) after oral administration of PEG 400 and SNEDDS in normal rats. (C) Microscopic observation of intestine (100×) after oral administration of PEG 400 and SNEDDS in normal rats. (D) Microscopic observation of stomach (100×) after oral administration of PEG 400 and SNEDDS in RYGB rats. (E) Microscopic observation of intestine (100×) after oral administration of PEG 400 and SNEDDS in RYGB rats. (F) Confocal imaging of stomach (100×) after oral administration of PEG 400 and SNEDDS in RYGB rats. (G) Confocal imaging of intestine (100×) after oral administration of PEG 400 and SNEDDS in RYGB rats. Triangles in (B–G) indicate the lumens.

Abbreviations: RYGB, Roux-en-Y gastric bypass; PEG, polyethylene glycol; SNEDDS, self-nanoemulsifying drug delivery systems.

Figure 5 Histopathological observation of stomach and intestine of rats after oral administration of Nile red-containing PEG 400 solution and SNEDDS.

Notes: (A) H&E staining of stomach (40×) after oral administration of PEG 400 and SNEDDS in normal rats. (B) H&E staining of intestine (100×) after oral administration of PEG 400 and SNEDDS in normal rats. The triangles indicate the lumens. (C) COX-2 staining of stomach (40×) after oral administration of PEG 400 and SNEDDS in normal rats. (D) COX-2 staining of intestine (100×) after oral administration of PEG 400 and SNEDDS in normal rats. The triangles and arrows in (A–C) indicate esophagus squamous epithelium and columnar epithelium, respectively.

Abbreviations: COX-2, cyclooxygenase-2; H&E, hematoxylin and eosin; PEG, polyethylene glycol; SNEDDS, self-nanoemulsifying drug delivery systems.