TY - JOUR
T1 - Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs
AU - Rathore, C.
AU - Upadhyay, N.
AU - Kaundal, R.
AU - Dwivedi, R. P.
AU - Rahatekar, S.
AU - John, A.
AU - Dua, K.
AU - Tambuwala, Murtaza
AU - Jain, S.
AU - Chaudari, D.
AU - Negi, P.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Background: The poor biopharmaceutical properties of thymoquinone (TQ) obstruct its development as a hepatoprotective agent. To surmount the delivery challenges of TQ, phospholipid nanoconstructs (PNCs) were constructed.
Method: PNCs were constructed employing microemulsification technique and systematic optimization by three-factor three level Box-Behnken design.
Result: Optimized PNC composition exhibited nano size (<100 nm), spherical morphology, within acceptable range of polydispersity index (0.55), high drug entrapment efficiency (>90%), controlled drug release pattern, and neutral surface charge (zeta potential of −0.65 mV). After oral administration of a single dose of PNC, it showed a relative bioavailability of 386.03% vis-à-vis plain TQ suspension. Further, TQ-loaded PNC demonstrated significant enhanced hepato-protective effect vis-à-vis pure TQ suspension and silymarin, as evidenced by reduction in the ALP, ALT, AST, bilirubin, and albumin level and ratified by histopathological analysis.
Conclusion: TQ-loaded PNCs can be efficient nano-platforms for the management of hepatic disorders and promising drug delivery systems to enhance oral bioavailability of this hydrophobic molecule.
AB - Background: The poor biopharmaceutical properties of thymoquinone (TQ) obstruct its development as a hepatoprotective agent. To surmount the delivery challenges of TQ, phospholipid nanoconstructs (PNCs) were constructed.
Method: PNCs were constructed employing microemulsification technique and systematic optimization by three-factor three level Box-Behnken design.
Result: Optimized PNC composition exhibited nano size (<100 nm), spherical morphology, within acceptable range of polydispersity index (0.55), high drug entrapment efficiency (>90%), controlled drug release pattern, and neutral surface charge (zeta potential of −0.65 mV). After oral administration of a single dose of PNC, it showed a relative bioavailability of 386.03% vis-à-vis plain TQ suspension. Further, TQ-loaded PNC demonstrated significant enhanced hepato-protective effect vis-à-vis pure TQ suspension and silymarin, as evidenced by reduction in the ALP, ALT, AST, bilirubin, and albumin level and ratified by histopathological analysis.
Conclusion: TQ-loaded PNCs can be efficient nano-platforms for the management of hepatic disorders and promising drug delivery systems to enhance oral bioavailability of this hydrophobic molecule.
KW - Thymoquinone
KW - box-Behnken design
KW - hepatotoxicity
KW - lipid carriers
KW - microemulsifcation
KW - pharmacokinetics
UR - https://pubmed.ncbi.nlm.nih.gov/32003249-enhanced-oral-bioavailability-and-hepatoprotective-activity-of-thymoquinone-in-the-form-of-phospholipidic-nano-constructs/?from_term=tambuwala&from_sort=pubdate&from_pos=2
UR - https://www.tandfonline.com/doi/full/10.1080/17425247.2020.1716728
UR - http://www.scopus.com/inward/record.url?scp=85078842656&partnerID=8YFLogxK
U2 - 10.1080/17425247.2020.1716728
DO - 10.1080/17425247.2020.1716728
M3 - Article
C2 - 32003249
SN - 1742-5247
VL - 17
SP - 237
EP - 253
JO - Expert Opinion on Drug Delivery
JF - Expert Opinion on Drug Delivery
IS - 2
ER -