TY - JOUR
T1 - Enhancement of Bioavailability and Pharmacodynamic Effects of Thymoquinone Via Nanostructured Lipid Carrier (NLC) Formulation
AU - Elmowafy, Mohammed
AU - Samy, Ahmed
AU - Raslan, Mohamed A.
AU - Salama, Ayman
AU - Said, Ragab A.
AU - Abdelaziz, Abdelaziz E.
AU - El-Eraky, Wafaa
AU - El Awdan, Sally
AU - Viitala, Tapani
N1 - Publisher Copyright:
© 2015, American Association of Pharmaceutical Scientists.
PY - 2016
Y1 - 2016
N2 - Thymoquinone (TQ), obtained from black cumin (Nigella sativa), is a natural product with anti-oxidant, anti-inflammatory, and hepatoprotective effects but unfortunately with poor bioavailability. Aiming to improve its poor oral bioavailability, TQ-loaded nanostructured lipid carriers (NLCs) were prepared by high-speed homogenization followed by ultrasonication and evaluated in vitro. Bioavailability and pharmacodynamic studies were also performed. The resultant NLCs showed poor physical homogeneity in Compritol 888 ATO Pluronic F127 system which consequently produced larger particle size and polydispersity index, smaller zeta potential values, and lower short-term (30 days) physical stability than other systems. Encapsulation efficiency percentage (EE%) lied between 84.6 ± 5% and 96.2 ± 1.6%. TQ AUC0–t values were higher in animals treated with NLCs, with a relative bioavailability of 2.03- and 3.97-fold (for F9 and F12, respectively) higher than TQ suspension, indicating bioavailability enhancement by NLC formulation. Hepatoprotective effects of F12 showed significant (P < 0.05) decrease in both serum alanine amino transferase and aspartate amino transferase to reach 305.0 ± 24.88 and 304.7 ± 23.55 U/ml, respectively, when compared with untreated toxic group. Anti-oxidant efficacy of F12 showed significant (P < 0.05) decline of malondialdehyde and elevation of reduced glutatione. This improvement was also confirmed histopathologically.
AB - Thymoquinone (TQ), obtained from black cumin (Nigella sativa), is a natural product with anti-oxidant, anti-inflammatory, and hepatoprotective effects but unfortunately with poor bioavailability. Aiming to improve its poor oral bioavailability, TQ-loaded nanostructured lipid carriers (NLCs) were prepared by high-speed homogenization followed by ultrasonication and evaluated in vitro. Bioavailability and pharmacodynamic studies were also performed. The resultant NLCs showed poor physical homogeneity in Compritol 888 ATO Pluronic F127 system which consequently produced larger particle size and polydispersity index, smaller zeta potential values, and lower short-term (30 days) physical stability than other systems. Encapsulation efficiency percentage (EE%) lied between 84.6 ± 5% and 96.2 ± 1.6%. TQ AUC0–t values were higher in animals treated with NLCs, with a relative bioavailability of 2.03- and 3.97-fold (for F9 and F12, respectively) higher than TQ suspension, indicating bioavailability enhancement by NLC formulation. Hepatoprotective effects of F12 showed significant (P < 0.05) decrease in both serum alanine amino transferase and aspartate amino transferase to reach 305.0 ± 24.88 and 304.7 ± 23.55 U/ml, respectively, when compared with untreated toxic group. Anti-oxidant efficacy of F12 showed significant (P < 0.05) decline of malondialdehyde and elevation of reduced glutatione. This improvement was also confirmed histopathologically.
KW - bioavailability
KW - hepatoprotective activity
KW - NLC
KW - thymoquinone
UR - http://www.scopus.com/inward/record.url?scp=84939818006&partnerID=8YFLogxK
U2 - 10.1208/s12249-015-0391-0
DO - 10.1208/s12249-015-0391-0
M3 - Article
C2 - 26304932
AN - SCOPUS:84939818006
SN - 1530-9932
VL - 17
SP - 663
EP - 672
JO - AAPS PharmSciTech
JF - AAPS PharmSciTech
IS - 3
ER -