Enhanced Permeation of Methotrexate via Loading into Ultra-permeable Niosomal Vesicles: Fabrication, Statistical Optimization, Ex Vivo Studies, and In Vivo Skin Deposition and Tolerability

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dc.contributor.author Al-mahallawi A.M.
dc.contributor.author Fares A.R.
dc.contributor.author Abd-Elsalam W.H.
dc.contributor.other Department of Pharmaceutics and Industrial Pharmacy
dc.contributor.other Faculty of Pharmacy
dc.contributor.other Cairo University
dc.contributor.other Kasr El-Ainy Street
dc.contributor.other Cairo
dc.contributor.other 11562
dc.contributor.other Egypt; Department of Pharmaceutics and Industrial Pharmacy
dc.contributor.other Faculty of Pharmacy
dc.contributor.other October University for Modern Science and Arts (MSA)
dc.contributor.other Giza
dc.contributor.other Egypt
dc.date.accessioned 2020-01-09T20:40:36Z
dc.date.available 2020-01-09T20:40:36Z
dc.date.issued 2019
dc.identifier.issn 15309932
dc.identifier.other https://doi.org/10.1208/s12249-019-1380-5
dc.identifier.other PubMed ID 31004239
dc.identifier.uri https://t.ly/GgZEX
dc.description Scopus
dc.description.abstract The aim of this study was to incorporate methotrexate (MTX) into ultra-permeable niosomal vesicles, containing cremophor RH40 as an edge activator (EA) and polyvinyl alcohol (PVA) as a stabilizer to enhance the drug permeation. Formulae were prepared by ethanol injection method following a Box-Behnken design in order to optimize the formulation variables (EA%, stabilizer %, and sonication time). To investigate the role of both cremophor RH40 and PVA, conventional MTX niosomes and MTX niosomes containing PVA only were fabricated. Drug entrapment efficiency percent (EE%), particle size (PS) analysis, zeta potential (ZP) measurements, and transmission electron microscopy (TEM) were conducted to characterize the vesicles. Cell viability studies and ex vivo permeation experiments of the optimized formula were conducted. Lastly, in vivo skin deposition of MTX from both the optimized formula and MTX solution was performed in rats. Besides, histopathological changes in rat skin were assessed. The optimized MTX ultra-permeable niosomal formula demonstrated spherical morphology, with an EE% of 65.16% and a PS of 453.6�nm. The optimized formula showed better physical stability in comparison with that of the same composition but lacking PVA. The cell viability studies verified the superior cytotoxicity of the optimized formula, and the ex vivo permeation studies revealed its ability to improve the drug permeation. The optimized formula demonstrated a significant deposition of MTX in rat dorsal skin, and histopathological evaluation confirmed the tolerability of the optimized formula in rats upon topical application. Accordingly, ultra-permeable noisomes, as a stable nanosystem, could be promising for effective delivery of MTX. � 2019, American Association of Pharmaceutical Scientists. en_US
dc.description.uri https://www.scimagojr.com/journalsearch.php?q=19374&tip=sid&clean=0
dc.language.iso English en_US
dc.publisher Springer New York LLC en_US
dc.relation.ispartofseries AAPS PharmSciTech
dc.relation.ispartofseries 20
dc.subject Box-Behnken design en_US
dc.subject edge activator en_US
dc.subject histopathology en_US
dc.subject IC 50 en_US
dc.subject methotrexate en_US
dc.subject niosomes en_US
dc.subject cremophor en_US
dc.subject methotrexate en_US
dc.subject niosome en_US
dc.subject polyvinyl alcohol en_US
dc.subject stabilizing agent en_US
dc.subject antineoplastic antimetabolite en_US
dc.subject liposome en_US
dc.subject methotrexate en_US
dc.subject animal experiment en_US
dc.subject animal tissue en_US
dc.subject Article en_US
dc.subject cell mediated cytotoxicity en_US
dc.subject cell structure en_US
dc.subject cell viability en_US
dc.subject controlled study en_US
dc.subject cytotoxicity en_US
dc.subject drug penetration en_US
dc.subject drug tolerability en_US
dc.subject encapsulation en_US
dc.subject ex vivo study en_US
dc.subject high performance liquid chromatography en_US
dc.subject histopathology en_US
dc.subject MCF-7 cell line en_US
dc.subject nonhuman en_US
dc.subject photon correlation spectroscopy en_US
dc.subject priority journal en_US
dc.subject rat en_US
dc.subject skin en_US
dc.subject skin surface en_US
dc.subject transmission electron microscopy en_US
dc.subject zeta potential en_US
dc.subject animal en_US
dc.subject cell survival en_US
dc.subject drug delivery system en_US
dc.subject drug effect en_US
dc.subject drug formulation en_US
dc.subject male en_US
dc.subject particle size en_US
dc.subject skin absorption en_US
dc.subject topical drug administration en_US
dc.subject Wistar rat en_US
dc.subject Administration, Topical en_US
dc.subject Animals en_US
dc.subject Antimetabolites, Antineoplastic en_US
dc.subject Cell Survival en_US
dc.subject Drug Compounding en_US
dc.subject Drug Delivery Systems en_US
dc.subject Liposomes en_US
dc.subject Male en_US
dc.subject Methotrexate en_US
dc.subject Particle Size en_US
dc.subject Rats en_US
dc.subject Rats, Wistar en_US
dc.subject Skin Absorption en_US
dc.title Enhanced Permeation of Methotrexate via Loading into Ultra-permeable Niosomal Vesicles: Fabrication, Statistical Optimization, Ex Vivo Studies, and In Vivo Skin Deposition and Tolerability en_US
dc.type Article en_US
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dcterms.source Scopus
dc.identifier.doi https://doi.org/10.1208/s12249-019-1380-5
dc.identifier.doi PubMed ID 31004239
dc.Affiliation October University for modern sciences and Arts (MSA)


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