Pharmacokinetics and Biodistribution of Thymoquinone-loaded Nanostructured Lipid Carrier After Oral and Intravenous Administration into Rats

Figures & data

Table 1 Physiochemical Characteristics of TQ-NLC After 24 Hours

Formulation	Z-Average (d, nm)	PDI	Zeta Potential (mV)	Temperature (°C)
TQ-NLC	37.84±0.287	0.19±0.003	−5.80±0.450	25

Note: Values are expressed as mean ±SD and measured in triplicates.

Abbreviations: PDI, polydispersity index; TQ-NLC, thymoquinone-loaded nanostructured lipid carrier.

Table 2 Free TQ Detected by HPLC at Wavelength of 254 Nm with Retention Time of 9.7 Minutes

Peak Name	Retention Time (minutes)	Area	% area	Height	Amount	Unit
Free TQ	9.742	11,336,968	100	79,130	9.64	mg/mL*

Note: *Thymoquinone quantity in mg/mL.

Abbreviations: HPLC, high-performance liquid chromatography; TQ, thymoquinone.

Figure 1 In vitro drug release profile of TQ-NLC and pure TQ solution. The release of TQ from TQ-NLC was lower than pure TQ solution.

Notes: * P<0.05, compared to pure TQ solution.

Abbreviations: TQ, thymoquinone; TQNLC, TQ-loaded nanostructured lipid carrier.

Table 3 Linear Regression of TQ-NLC Release Kinetic by Mathematical Modelling Using Various Drug Kinetic Models

Kinetic Model	Correlation Coefficient (R^Citation2) Value
Zero-order	0.9710
First-order	0.5708
Higuchi	0.9328
Hixson–Crowell	0.7627

Abbreviation: TQ-NLC, thymoquinone-loaded nanostructured lipid carrier.

Figure 2 Linear regression of TQ-NLC release kinetic by using Korsmeyer–Peppas equation. The value of n was determined from the gradient of the linear line.

Abbreviation: TQ-NLC, thymoquinone-loaded nanostructured lipid carrier.

Table 4 Optimisation of Stannous Chloride Amount

Amount of Stannous Chloride (µg/mL)	% Drug Labeled (mean ±SD)
50	95.69±0.559
150	97.20±0.115
300	92.00±1.804
450	89.53±2.198
600	69.67±1.859

Note: Values are expressed as mean ±SD and measured in triplicates.

Table 5 Stability of ^99mTc-TQ-NLC at Room Temperature and in Rat Serum

Time (hours)	%Labelling Efficiency (mean ±SD)
	Room Temperature	Rat Serum
0.5	97.22±0.210	97.22±0.210
1	93.30±1.084	80.41±1.560
2	91.38±0.445	76.19±1.413
4	91.27±0.053	69.05±2.273
6	84.01±1.219	66.87±1.307
8	74.35±2.324	58.35±2.616
24	33.43±1.579	14.92±2.773

Note: Values are expressed as mean ±SD and measured in triplicates.

Abbreviations: ^99mTc, technetium-99m; TQ-NLC, thymoquinone-loaded nanostructured lipid carrier.

Table 6 Pharmacokinetics Parameters for ^99mTc-TQ-NLC After Oral and Intravenous Administrations into Rats (n=6)

Parameters	Oral Administration		Intravenous Administration
	Plasma	Blood	Plasma	Blood
Tmax (h)	4	4	0.5	0.5
Cmax (%ID/g)	0.413	0.347	3.284	2.173
AUC24 (%ID/g.h)	1.708	1.404	7.847	4.947
AUC0-∞ (%ID/g.h)	1.762	1.453	7.998	5.089
AUCexp (%ID/g.h)	3.077	3.384	1.889	2.788
t1/2 (h)	2.457	2.386	4.992	5.336
CL (L/h)	56.735	68.87	12.503	19.649
Relative bioavailability (%)	201.125	236.813	90.037	151.259

Abbreviations: AUC₂₄, 24 h area under the curve concentration-time; AUC_0-∞, area under the curve to infinity; AUC_exp; exponential area under the curve; C_max, the maximum concentration; CL, clearance; ID/g, injected dose per gram; h, hour; ^99mTc, technetium-99m; TQ-NLC, thymoquinone-loaded nanostructured lipid carrier; T_max, the time taken to reach the maximum concentration; t_1/2, half-life.

Figure 3 Time profile of ^99mTc-TQ-NLC in blood after the oral and intravenous administration into rats (n=6).

Abbreviations:^99mTc, technetium-99m; TQ-NLC, thymoquinone-loaded nanostructured lipid carrier; ID/g, injected dose per gram.

Figure 4 (A) Images of rats administered with ^99mTc-TQ-NLC. Gamma camera in vivo data were acquired along 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h after the oral administration. (B) Intestine to blood ratios. (C) Intestine to muscle ratios. (D) Liver to blood ratios. (E) Liver to muscle ratios. (F) Kidneys to blood ratios. (G) Kidneys to muscle ratios.

Notes: Values are expressed as mean ±SD, n=6. Mean values with different letters are significantly different (P <0.05).

Abbreviations:^99mTc, technetium-99m; TQ-NLC, thymoquinone-loaded nanostructured lipid carrier.

Figure 5 (A) Images of rats administered with ^99mTc-TQ-NLC. Gamma camera in vivo data were acquired along 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h after the intravenous administration. (B) Intestine to blood ratios. (C) Intestine to muscle ratios. (D) Liver to blood ratios. (E) Liver to muscle ratios. (F) Kidneys to blood ratios. (G) Kidneys to muscle ratios.

Notes: Values are expressed as mean ±SD, n=6. Mean values with different letters are significantly different (P <0.05).

Abbreviations:^99mTc, technetium-99m; TQ-NLC, thymoquinone-loaded nanostructured lipid carrier.

Figure 6 Biodistribution data showing uptake (% ID/g) of organs vs time profile after the oral administration with ^99mTc-TQ-NLC (n=6).

Abbreviations:^99mTc, technetium-99m; TQ-NLC, thymoquinone-loaded nanostructured lipid carrier; ID/g, injected dose per gram.

Figure 7 Biodistribution data showing uptake (% ID/g) of organs vs time profile after the intravenous administration with ^99mTc-TQ-NLC (n=6).

Abbreviations:^99mTc, technetium-99m; TQ-NLC, thymoquinone-loaded nanostructured lipid carrier; ID/g, injected dose per gram.

Lerisko-iversidge EM, Liversidge GG. Drug Nanoparticles: formulating Poorly Water-Soluble Compounds. Toxicol Pathol. 2008;36:43–48. doi:10.1177/019262330731094618337220

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