Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs

C. Rathore, N. Upadhyay, R. Kaundal, R. P. Dwivedi, S. Rahatekar, A. John, K. Dua, Murtaza Tambuwala, S. Jain, D. Chaudari, P. Negi

    Research output: Contribution to journalArticle

    Abstract

    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.
    LanguageEnglish
    Pages1-17
    Number of pages7
    JournalExpert Opinion on Drug Delivery
    Early online date31 Jan 2020
    DOIs
    Publication statusE-pub ahead of print - 31 Jan 2020

    Fingerprint

    Biological Availability
    Phospholipids
    Suspensions
    Silymarin
    Drug Delivery Systems
    Bilirubin
    Oral Administration
    thymoquinone
    Albumins
    Liver

    Keywords

    • Thymoquinone
    • box-Behnken design
    • lipid carriers
    • microemulsifcation
    • hepatotoxicity
    • pharmacokinetics

    Cite this

    Rathore, C. ; Upadhyay, N. ; Kaundal, R. ; Dwivedi, R. P. ; Rahatekar, S. ; John, A. ; Dua, K. ; Tambuwala, Murtaza ; Jain, S. ; Chaudari, D. ; Negi, P. / Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs. In: Expert Opinion on Drug Delivery. 2020 ; pp. 1-17.
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    abstract = "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-{\`a}-vis plain TQ suspension. Further, TQ-loaded PNC demonstrated significant enhanced hepato-protective effect vis-{\`a}-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.",
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    author = "C. Rathore and N. Upadhyay and R. Kaundal and Dwivedi, {R. P.} and S. Rahatekar and A. John and K. Dua and Murtaza Tambuwala and S. Jain and D. Chaudari and P. Negi",
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    Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs. / Rathore, C.; Upadhyay, N.; Kaundal, R.; Dwivedi, R. P.; Rahatekar, S.; John, A.; Dua, K.; Tambuwala, Murtaza; Jain, S.; Chaudari, D.; Negi, P.

    In: Expert Opinion on Drug Delivery, 31.01.2020, p. 1-17.

    Research output: Contribution to journalArticle

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    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 - 2020/1/31

    Y1 - 2020/1/31

    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.

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