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.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorAl-mahallawi A.M.
dc.contributor.authorFares A.R.
dc.contributor.authorAbd-Elsalam W.H.
dc.contributor.otherDepartment of Pharmaceutics and Industrial Pharmacy
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherCairo University
dc.contributor.otherKasr El-Ainy Street
dc.contributor.otherCairo
dc.contributor.other11562
dc.contributor.otherEgypt; Department of Pharmaceutics and Industrial Pharmacy
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherOctober University for Modern Science and Arts (MSA)
dc.contributor.otherGiza
dc.contributor.otherEgypt
dc.date.accessioned2020-01-09T20:40:36Z
dc.date.available2020-01-09T20:40:36Z
dc.date.issued2019
dc.descriptionScopus
dc.description.abstractThe 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.urihttps://www.scimagojr.com/journalsearch.php?q=19374&tip=sid&clean=0
dc.identifier.doihttps://doi.org/10.1208/s12249-019-1380-5
dc.identifier.doiPubMed ID 31004239
dc.identifier.issn15309932
dc.identifier.otherhttps://doi.org/10.1208/s12249-019-1380-5
dc.identifier.otherPubMed ID 31004239
dc.identifier.urihttps://t.ly/GgZEX
dc.language.isoEnglishen_US
dc.publisherSpringer New York LLCen_US
dc.relation.ispartofseriesAAPS PharmSciTech
dc.relation.ispartofseries20
dc.subjectBox-Behnken designen_US
dc.subjectedge activatoren_US
dc.subjecthistopathologyen_US
dc.subjectIC 50en_US
dc.subjectmethotrexateen_US
dc.subjectniosomesen_US
dc.subjectcremophoren_US
dc.subjectmethotrexateen_US
dc.subjectniosomeen_US
dc.subjectpolyvinyl alcoholen_US
dc.subjectstabilizing agenten_US
dc.subjectantineoplastic antimetaboliteen_US
dc.subjectliposomeen_US
dc.subjectmethotrexateen_US
dc.subjectanimal experimenten_US
dc.subjectanimal tissueen_US
dc.subjectArticleen_US
dc.subjectcell mediated cytotoxicityen_US
dc.subjectcell structureen_US
dc.subjectcell viabilityen_US
dc.subjectcontrolled studyen_US
dc.subjectcytotoxicityen_US
dc.subjectdrug penetrationen_US
dc.subjectdrug tolerabilityen_US
dc.subjectencapsulationen_US
dc.subjectex vivo studyen_US
dc.subjecthigh performance liquid chromatographyen_US
dc.subjecthistopathologyen_US
dc.subjectMCF-7 cell lineen_US
dc.subjectnonhumanen_US
dc.subjectphoton correlation spectroscopyen_US
dc.subjectpriority journalen_US
dc.subjectraten_US
dc.subjectskinen_US
dc.subjectskin surfaceen_US
dc.subjecttransmission electron microscopyen_US
dc.subjectzeta potentialen_US
dc.subjectanimalen_US
dc.subjectcell survivalen_US
dc.subjectdrug delivery systemen_US
dc.subjectdrug effecten_US
dc.subjectdrug formulationen_US
dc.subjectmaleen_US
dc.subjectparticle sizeen_US
dc.subjectskin absorptionen_US
dc.subjecttopical drug administrationen_US
dc.subjectWistar raten_US
dc.subjectAdministration, Topicalen_US
dc.subjectAnimalsen_US
dc.subjectAntimetabolites, Antineoplasticen_US
dc.subjectCell Survivalen_US
dc.subjectDrug Compoundingen_US
dc.subjectDrug Delivery Systemsen_US
dc.subjectLiposomesen_US
dc.subjectMaleen_US
dc.subjectMethotrexateen_US
dc.subjectParticle Sizeen_US
dc.subjectRatsen_US
dc.subjectRats, Wistaren_US
dc.subjectSkin Absorptionen_US
dc.titleEnhanced Permeation of Methotrexate via Loading into Ultra-permeable Niosomal Vesicles: Fabrication, Statistical Optimization, Ex Vivo Studies, and In Vivo Skin Deposition and Tolerabilityen_US
dc.typeArticleen_US
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