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

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...

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Autores principales:	Salem HF, Nafady MM, Kharshoum RM, Abd el-Ghafar OA, Farouk HO
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	ssris nano carrier via skin pharmacokinetic parameters autoimmune disease rankl Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e17950f512cd44c389c8094523cec793
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spelling	oai:doaj.org-article:e17950f512cd44c389c8094523cec7932021-12-02T10:35:48ZMitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment1178-2013https://doaj.org/article/e17950f512cd44c389c8094523cec7932020-03-01T00:00:00Zhttps://www.dovepress.com/mitigation-of-rheumatic-arthritis-in-a-rat-model-via-transdermal-deliv-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Heba 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, EgyptCorrespondence: Heba Farouk SalemPharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Beni- Suef University, Beni Suef city, EgyptTel +2 01001944381Email heba_salem2004@yahoo.co.ukPurpose: 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, RANKLSalem HFNafady MMKharshoum RMAbd el-Ghafar OAFarouk HODove Medical Pressarticlessrisnano carrier via skinpharmacokinetic parametersautoimmune diseaseranklMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1517-1535 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	ssris nano carrier via skin pharmacokinetic parameters autoimmune disease rankl Medicine (General) R5-920
spellingShingle	ssris nano carrier via skin pharmacokinetic parameters autoimmune disease rankl Medicine (General) R5-920 Salem HF Nafady MM Kharshoum RM Abd el-Ghafar OA Farouk HO Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment
description	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, EgyptCorrespondence: Heba Farouk SalemPharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Beni- Suef University, Beni Suef city, EgyptTel +2 01001944381Email heba_salem2004@yahoo.co.ukPurpose: 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
format	article
author	Salem HF Nafady MM Kharshoum RM Abd el-Ghafar OA Farouk HO
author_facet	Salem HF Nafady MM Kharshoum RM Abd el-Ghafar OA Farouk HO
author_sort	Salem HF
title	Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment
title_short	Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment
title_full	Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment
title_fullStr	Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment
title_full_unstemmed	Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment
title_sort	mitigation of rheumatic arthritis in a rat model via transdermal delivery of dapoxetine hcl amalgamated as a nanoplatform: in vitro and in vivo assessment
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/e17950f512cd44c389c8094523cec793
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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

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