Thymoquinone-loaded Self-nano-emulsifying Drug Delivery System Against Ischemia/reperfusion Injury

Overview

Journal Drug Deliv Transl Res

Publisher Springer

Specialty Pharmacology

Date 2023 Jul 31

PMID 37523093

Authors

Badr Bahloul

Roua Chaabani

Yosri Zahra

Nesrine Kalboussi

Jamil Kraiem

Souad Sfar

Nathalie Mignet

Hassen Ben Abdennebi

Affiliations

Soon will be listed here.

Abstract

In the present study, a self-nano-emulsifying drug delivery system (SNEDDS) was developed to evaluate the efficiency of thymoquinone (TQ) in hepatic ischemia/reperfusion. SNEDDS was pharmaceutically characterized to evaluate droplet size, morphology, zeta potential, thermodynamic stability, and dissolution/diffusion capacity. Animals were orally pre-treated during 10 days with TQ-loaded SNEDDS. Biochemical analyses, hematoxylin-eosin staining, indirect immunofluorescence, and reverse transcription polymerase chain reaction (RT-PCR) were carried out to assess cell injury, oxidative stress, inflammation, and apoptosis. The TQ formulation showed good in vitro characteristics, including stable nanoparticle structure and size with high drug release rate. In vivo determinations revealed that TQ-loaded SNEDDS pre-treatment of rats maintained cellular integrity by decreasing transaminase (ALT and AST) release and preserving the histological characteristics of their liver. The antioxidant ability of the formulation was proven by increased SOD activity, reduced MDA concentration, and iNOS protein expression. In addition, this formulation exerted an anti-inflammatory effect evidenced by reduced plasma CRP concentration, MPO activity, and gene expressions of TLR-4, TNF-α, NF-κB, and IL-6. Finally, the TQ-loaded SNEDDS formulation promoted cell survival by enhancing the Bcl-2/Bax ratio. In conclusion, our results indicate that TQ encapsulated in SNEDDS significantly protects rat liver from I/R injury.

Citing Articles

Self-Emulsifying Drug Delivery Systems (SEDDS): Transition from Liquid to Solid-A Comprehensive Review of Formulation, Characterization, Applications, and Future Trends.

Uttreja P, Karnik I, Youssef A, Narala N, Elkanayati R, Baisa S Pharmaceutics. 2025; 17(1).

PMID: 39861711 PMC: 11768142. DOI: 10.3390/pharmaceutics17010063.

References

Choi H, Kim H, Sakong J . Rates and subsequent clinical course of fetal congenital anomalies detected by prenatal targeted ultrasonography of 137 cases over 5 years in a single institute: a retrospective observational study. J Yeungnam Med Sci. 2022; 40(3):268-275. PMC: 10390279. DOI: 10.12701/jyms.2022.00514. View

Mendes-Braz M, Elias-Miro M, Jimenez-Castro M, Casillas-Ramirez A, Ramalho F, Peralta C . The current state of knowledge of hepatic ischemia-reperfusion injury based on its study in experimental models. J Biomed Biotechnol. 2012; 2012:298657. PMC: 3357607. DOI: 10.1155/2012/298657. View

Quesnelle K, Bystrom P, Toledo-Pereyra L . Molecular responses to ischemia and reperfusion in the liver. Arch Toxicol. 2015; 89(5):651-7. DOI: 10.1007/s00204-014-1437-x. View

Wiggins B, Saseen J, Page 2nd R, Reed B, Sneed K, Kostis J . Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2016; 134(21):e468-e495. DOI: 10.1161/CIR.0000000000000456. View

Gaire B . Herbal Medicine in Ischemic Stroke: Challenges and Prospective. Chin J Integr Med. 2018; 24(4):243-246. DOI: 10.1007/s11655-018-2828-2. View

Sharifpanah F, Ali E, Wartenberg M, Sauer H . The milk thistle (Silybum marianum) compound Silibinin stimulates leukopoiesis from mouse embryonic stem cells. Phytother Res. 2018; 33(2):452-460. DOI: 10.1002/ptr.6241. View

Sedighi M, Sewell R, Nazari A, Abbaszadeh S, Cheraghi M, Amini A . A Review on the Most Important Medicinal Plants Effective in Cardiac Ischemia-Reperfusion Injury. Curr Pharm Des. 2019; 25(3):352-358. DOI: 10.2174/1381612825666190329144016. View

Ali M, Ahmad R, Leyla F, Reza Y, Taghi R . A case of misdiagnose of malaria infection. Asian Pac J Trop Biomed. 2013; 3(9):748-50. PMC: 3757286. DOI: 10.1016/S2221-1691(13)60150-1. View

Gholamnezhad Z, Havakhah S, Boskabady M . Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. J Ethnopharmacol. 2016; 190:372-86. DOI: 10.1016/j.jep.2016.06.061. View

10.

Rathore C, Rathbone M, Chellappan D, Tambuwala M, Pinto T, Dureja H . Nanocarriers: more than tour de force for thymoquinone. Expert Opin Drug Deliv. 2020; 17(4):479-494. DOI: 10.1080/17425247.2020.1730808. View

11.

Darakhshan S, Bidmeshki Pour A, Hosseinzadeh Colagar A, Sisakhtnezhad S . Thymoquinone and its therapeutic potentials. Pharmacol Res. 2015; 95-96:138-58. DOI: 10.1016/j.phrs.2015.03.011. View

12.

Bouhlel A, Ben Mosbah I, Hadj Abdallah N, Ribault C, Viel R, Mannai S . Thymoquinone prevents endoplasmic reticulum stress and mitochondria-induced apoptosis in a rat model of partial hepatic warm ischemia reperfusion. Biomed Pharmacother. 2017; 94:964-973. DOI: 10.1016/j.biopha.2017.08.018. View

13.

Bouhlel A, Bejaoui M, Ben Mosbah I, Hadj Abdallah N, Ribault C, Viel R . Thymoquinone protects rat liver after partial hepatectomy under ischaemia/reperfusion through oxidative stress and endoplasmic reticulum stress prevention. Clin Exp Pharmacol Physiol. 2018; . DOI: 10.1111/1440-1681.12961. View

14.

Kooti W, Hasanzadeh-Noohi Z, Sharafi-Ahvazi N, Asadi-Samani M, Ashtary-Larky D . Phytochemistry, pharmacology, and therapeutic uses of black seed (Nigella sativa). Chin J Nat Med. 2017; 14(10):732-745. DOI: 10.1016/S1875-5364(16)30088-7. View

15.

Bahloul B, Lassoued M, Sfar S . A novel approach for the development and optimization of self emulsifying drug delivery system using HLB and response surface methodology: application to fenofibrate encapsulation. Int J Pharm. 2014; 466(1-2):341-8. DOI: 10.1016/j.ijpharm.2014.03.040. View

16.

Bahloul B, Lassoued M, Seguin J, Lai-Kuen R, Dhotel H, Sfar S . Self-emulsifying drug delivery system developed by the HLB-RSM approach: Characterization by transmission electron microscopy and pharmacokinetic study. Int J Pharm. 2015; 487(1-2):56-63. DOI: 10.1016/j.ijpharm.2015.04.018. View

17.

Balakrishnan P, Lee B, Oh D, Kim J, Lee Y, Kim D . Enhanced oral bioavailability of Coenzyme Q10 by self-emulsifying drug delivery systems. Int J Pharm. 2009; 374(1-2):66-72. DOI: 10.1016/j.ijpharm.2009.03.008. View

18.

Bachhav Y, Patravale V . Microemulsion-based vaginal gel of clotrimazole: formulation, in vitro evaluation, and stability studies. AAPS PharmSciTech. 2009; 10(2):476-81. PMC: 2690796. DOI: 10.1208/s12249-009-9233-2. View

19.

Klang V, Valenta C, Matsko N . Electron microscopy of pharmaceutical systems. Micron. 2012; 44:45-74. DOI: 10.1016/j.micron.2012.07.008. View

20.

Hosseinzadeh H, Ziaee T, Sadeghi A . The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats. Phytomedicine. 2007; 15(6-7):491-5. DOI: 10.1016/j.phymed.2007.09.020. View