Optimization of Thymoquinone-Loaded Self-Nanoemulsion for Management of Indomethacin-Induced Ulcer

Mohamed F Radwan; Mohamed A El-Moselhy; Walied M Alarif; Mohamed Orif; Nabil K Alruwaili; Nabil A Alhakamy

doi:10.1177/15593258211013655

Optimization of Thymoquinone-Loaded Self-Nanoemulsion for Management of Indomethacin-Induced Ulcer

Dose Response. 2021 May 10;19(2):15593258211013655. doi: 10.1177/15593258211013655. eCollection 2021 Apr-Jun.

Authors

Mohamed F Radwan¹, Mohamed A El-Moselhy², Walied M Alarif³, Mohamed Orif³, Nabil K Alruwaili⁴, Nabil A Alhakamy^{5

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Affiliations

¹ Department of Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
² Department of Pharmacology, School of Pharmacy, Ibn Sina National College, Jeddah, Saudi Arabia.
³ Department of Marine Chemistry, Faculty of Marine Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Department of Pharmaceutics, Faculty of Pharmacy, Al-Jouf University, Sakaka, Saudi Arabia.
⁵ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
⁶ Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia.
⁷ Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

To improve the water solubility of thymoquinone (TQ), a major constituent of Nigella sativa seed oil, a TQ-loaded self-nanoemulsifying drug delivery system (SNEDDS) was prepared. The SNEDDS formulation was optimized using almond oil (AO) (Oil; X1), tween 80 (surfactant; X2) and polyethylene glycol 200 (PEG 200) (cosurfactant; X3) compounds as independent variables. The results showed that the globule size ranged from 65 to 320 nm. In addition, a strong agreement was reached between the system estimation and the experimental values of globule size. To evaluate the gastroprotective effect of optimized TQ-loaded SNEDDS against indomethacin (Indo.)-induced gastric ulcers in comparison with non-emulsified TQ, the ulcer index and histopathological changes were estimated. Optimized TQ-loaded SNEDDS showed improved gastroprotective activity against Indo.-induced ulcers relative to the non-emulsified TQ. In addition, the gastroprotective index was improved by 2-fold in TQ-loaded SNEDDS as compared to non-emulsified TQ. This is attributed to the strong antioxidant and the cytoprotective activities of the TQ. These results demonstrate enhancement of the efficacy of TQ through the optimized SNEDDS.

Keywords: almond oil; drug delivery; mixture design; peptic ulcer; self-nanoemulsifying drug delivery system; thymoquinone.