Contents lists available at ScienceDirect Journal of Drug Delivery Science and Technology journal homepage: www.elsevier.com/locate/jddst Transfersomal gel nanocarriers for enhancement the permeation of lornoxicam Hesham M. Tawfeek a,* , Ahmed A.H. Abdellatif b,c , Jelan A. Abdel-Aleem a , Yasser A. Hassan d,e , Dina Fathalla f a Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt b Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Al-Azhar University, 71524, Assiut, Egypt c Pharmaceutics Department, College of Pharmacy, Qassim University, 51452, Buraydah, Saudi Arabia d Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Dakhlia, Egypt e Department of Pharmaceutics, College of Pharmacy, Al-Bayan University, Baghdad, Iraq f Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt ARTICLE INFO Keywords: Lornoxicam Topical hydrogel Transfersomes Hydroxypropyl methylcellulose Ex vivo permeation ABSTRACT In respect to the major gastrointestinal disorders associated with oral administration of Lornoxicam, LOR, a potent anti-inflammatory drug, topical delivery could be an alternative route of administration. The objective of this work was to formulate LOR in the form of topical hydrogel after encapsulation into deformable vesicles, transfersomes, TRSs for maximum penetration and activity. LOR TRSs were prepared through thin film hydration technique and characterized for their encapsulation efficiency, size, charge, morphology and stability. Furthermore, LOR transfersomal and non-transfersomal hy- drogels were prepared using different gelling agents and characterized for their pH, contents, viscosity, homogeneity, skin irritation, in vitro release, skin permeation, and pharmacodynamic activity. Results revealed that optimum LOR TRSs had an encapsulation efficiency of 99.34 ± 0.2%, size of 233.5 ± 12.5 nm and zeta potential of -35.34 ± 0.78 mV. Furthermore, they showed higher chemical and physical stability when stored in the fridge. Transfersomal hydrogels stabilized with sodium deoxycholate showed higher drug permeation through rat skin. In addition, they have higher flux and apparent permeability coefficient and superior anti-inflammatory activity compared to non-transfersomal LOR hydrogel and in- domethacin gel as a standard NSAID. These findings confirmed that LOR transfersomal hydrogel is a promising topical formulation for effective treatment of local inflammatory conditions. 1. Introduction Oral non-steroidal anti-inflammatory drugs (NSAIDs) are most widely used for the healing of acute and chronic pain disorders [1]. However, their chronic usage may be associated with serious systemic side effects, especially gastrointestinal disorders, such as nausea, diar- rhea, and ulceration. In addition, some severe side effects including bronchospasms, bleeding, and the rare Stevens-Johnson syndrome [2]. One of the most potent and widely used NSAIDs is lornoxicam, LOR. It is a powerful inhibitor of both COX-1 and COX-2 enzymes [3]. In ad- dition, LOR has confirmed higher clinical efficacy in reducing chronic pain accompanying with osteoarthritis [4], rheumatoid arthritis, and ankylosing spondylitis [5,6]. Moreover, for the healing of postoperative pain, lornoxicam has been shown to be as efficient as morphine [7]. It has a half-life ranged from 3 to 5 h and peak plasma concentration is attained within 2.5 h. LOR is ten times more potent than other oxime derivatives [8]. However, like other NSAIDs, LOR still has an issue associated with its oral delivery on the gastrointestinal tract as the only marketed route of administration. Previously, LOR was formulated into mini-tablets and rectal suppositories [9,10]. However, oral tablets still showed the gastric effect and rectal suppositories might be unsuitable for some patients. LOR was formulated in the form of sustained release buccal patches for treatment of patients suffering from post-operative pain and edema following maxillofacial operations [11]. However, the inconvenient nature associated with these patches administration, especially with elderly people and children, is considered a problem. Moreover, the patients cannot eat, drink or even speak when using these patches for prolonged period of time. Swallowing of saliva may https://doi.org/10.1016/j.jddst.2020.101540 Received 12 November 2019; Received in revised form 4 January 2020; Accepted 22 January 2020 * Corresponding author. Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt. Tel.: 002 0882411322. E-mail addresses: Heshamtawfeek@aun.edu.eg, heshamtawfeek79@gmail.com (H.M. Tawfeek). Journal of Drug Delivery Science and Technology 56 (2020) 101540 Available online 27 January 2020 1773-2247/ © 2020 Elsevier B.V. All rights reserved. T