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Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment

Authors Salem HF, Nafady MM, Kharshoum RM, Abd el-Ghafar OA, Farouk HO

Received 15 November 2019

Accepted for publication 1 February 2020

Published 6 March 2020 Volume 2020:15 Pages 1517—1535

DOI https://doi.org/10.2147/IJN.S238709

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster


Heba Farouk Salem,1 Mohamed Mahmoud Nafady,2 Rasha Mostafa Kharshoum,1 Omnia Ahmed Abd el-Ghafar,3 Hanan Osman Farouk2

1Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Beni- Suef University, Beni Suef, Egypt; 2Pharmaceutics and Clinical Pharmacy Department, Faculty of Pharmacy, Nahda University, Beni Suef, Egypt; 3Pharmacology Department, Faculty of Pharmacy, Nahda University, Beni Suef, Egypt

Correspondence: Heba Farouk Salem
Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Beni- Suef University, Beni Suef city, Egypt
Tel +2 01001944381
Email heba_salem2004@yahoo.co.uk

Purpose: Dapoxetine HCl (DH), a selective serotonin reuptake inhibitor, may be useful for the treatment of rheumatic arthritis (RA). The purpose of this study was to investigate the therapeutic efficacy of transdermal delivery of DH in transethosome nanovesicles (TENVs). This novel delivery of DH may overcome the drawbacks associated with orally administered DH and improve patient compliance.
Methods: DH-TENV formulations were prepared using an injection- sonication method and optimized using a 33 Box-Behnken-design with Design Expert® software. The TENV formulations were assessed for entrapment efficiency (EE-%), vesicle size, zeta potential, in vitro DH release, and skin permeation. The tolerability of the optimized DH-TENV gel was investigated using a rat skin irritation test. A pharmacokinetic analysis of the optimized DH-TENV gel was also conducted in rats. Moreover, the anti-RA activity of the optimized DH-TENV gel was assessed based on the RA-specific marker anti-cyclic cirtullinated peptide antibody (anti-CCP), the cartilage destruction marker cartilage oligomeric matrix protein (COMP) and the inflammatory marker interleukin-6 (IL-6). Level of tissue receptor activator of nuclear factor kappa-&Bgr; ligand (RANKL) were also assessed.
Results: The optimized DH-TENV formulation involved spherical nanovesicles that had an appropriate EE- % and skin permeation characteristic. The DH-TENV gel was well tolerated by rats. The pharmacokinetics analysis showed that the optimized DH-TENV gel boosted the bioavailability of the DH by 2.42- and 4.16-fold compared to the oral DH solution and the control DH gel, respectively. Moreover, it significantly reduced the serum anti-CCP, COMP and IL-6 levels and decreased the RANKL levels. Furthermore, the DH-TENV gel attenuated histopathological changes by almost normalizing the articular surface and synovial fluid.
Conclusion: The results indicate that DH-TENVs can improve transdermal delivery of DH and thereby alleviate RA.

Keywords: SSRIs, nano carrier via skin, pharmacokinetic parameters, autoimmune disease, RANKL

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