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Abeer S Hassan,1 Amal Hofni,2 Mohammed AS Abourehab,3 Iman AM Abdel-Rahman4 1Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, Egypt; 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, South Valley University, Qena, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Minia University, Minia, Egypt; 4Department of Pharmacognosy, Faculty of Pharmacy, South Valley University, Qena, EgyptCorrespondence: Abeer S Hassan, Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, Egypt, Tel +201012060262, Email abeer.saad@svu.edu.egIntroduction: Ginger extract (GE) has sparked great interest due to its numerous biological benefits. However, it suffers from limited skin permeability, which challenges its transdermal application. The target of the current work was to develop transethosomes as a potential nanovehicle to achieve enhanced transdermal delivery of GE through the skin.Methods: GE–loaded transethosomes were prepared by cold injection using different edge activators. The fabricated nanovesicles were evaluated for particle size, ζ-potential, encapsulation efficiency, and in vitro drug release. The selected formulation was then laden into the hydrogel system and evaluated for ex vivo permeability and in vivo anti-inflammatory activity in a carrageenan-induced rat-paw edema model.Results: The selected formulation comprised of sodium deoxycholate exhibited particle size of 188.3± 7.66 nm, ζ-potential of − 38.6± 0.08 mV, and encapsulation efficiency of 91.0%± 0.24%. The developed transethosomal hydrogel containing hydroxypropyl methylcellulose was homogeneous, pseudoplastic, and demonstrated sustained drug release. Furthermore, it exhibited improved flux (12.61± 0.45 μg.cm2/second), apparent skin permeability (2.43± 0.008× 10− 6 cm/second), and skin deposition compared to free GE hydrogel. In vivo testing and histopathological examination revealed that the GE transethosomal hydrogel exhibited significant inhibition of edema swelling compared to free GE hydrogel and ketoprofen gel. The animals that were treated with ginger transethosome hydrogel showed a significant decrement in reactive oxygen species and prostaglandin E2 compared to untreated animals.Conclusion: Transethosomes might be a promising new vehicle for GE for effective skin permeation and anti-inflammation. To the best of our knowledge, this work is the first utilization of transethosomes laden into hydrogel as a novel transdermal delivery system of GE.Graphical Abstract: Keywords: nanovesicles, transethosomes, ginger, ex vivo permeation, transdermal delivery, inflammation |