000873827 001__ 873827
000873827 005__ 20210130004520.0
000873827 0247_ $$2doi$$a10.1016/j.ijpharm.2020.119057
000873827 0247_ $$2ISSN$$a0378-5173
000873827 0247_ $$2ISSN$$a1873-3476
000873827 0247_ $$2Handle$$a2128/24353
000873827 0247_ $$2altmetric$$aaltmetric:75458832
000873827 0247_ $$2pmid$$apmid:31991188
000873827 0247_ $$2WOS$$aWOS:000519297300044
000873827 037__ $$aFZJ-2020-01031
000873827 082__ $$a610
000873827 1001_ $$0P:(DE-HGF)0$$aPuig-Rigall, Joan$$b0
000873827 245__ $$aStructural characterization by scattering and spectroscopic methods and biological evaluation of polymeric micelles of poloxamines and TPGS as nanocarriers for miltefosine delivery
000873827 260__ $$aNew York, NY [u.a.]$$bElsevier$$c2020
000873827 3367_ $$2DRIVER$$aarticle
000873827 3367_ $$2DataCite$$aOutput Types/Journal article
000873827 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1582092242_3364
000873827 3367_ $$2BibTeX$$aARTICLE
000873827 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000873827 3367_ $$00$$2EndNote$$aJournal Article
000873827 520__ $$aMiltefosine (MF), an alkylphospholipid originally developed for breast cancer treatment, is a highly active drug for the treatment against leishmaniasis, a neglected tropical disease considered the world’s second leading cause of death by a parasitic agent after malaria. MF exhibits dose-limiting gastrointestinal side effects in patients and its penetration through lipophilic barriers is reduced. In this work we propose a reformulation of MF by incorporating the drug to poly(ethylene)oxide (PEO)-based polymeric micelles, specifically, D-α-tocopheryl polyethylene glycol succinate (TPGS) and Tetronic block copolymers (T904 and T1107). A full structural characterization of the aggregates has been carried out by SANS (small-angle neutron scattering) and dynamic light scattering (DLS), in combination with proton 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, to determine the precise location of the drug. The structure of MF micelles has been characterized as a function of the temperature and concentration. In the presence of the block-copolymers, MF forms mixed micelles in a wide range of temperatures, TPGS being the co-surfactant that incorporates more MF unimers. The hydrophobic tail of MF and those of the block copolymers are in close contact within the micelles, which present a core-shell structure with a hydrophilic corona formed by the PEG blocks of the TPGS and the zwitterion head group of the MF. In order to identify the best carrier, the antileishmanicidal activity of MF in the different formulations has been tested on macrophages, promastigotes and intracellular amastigotes. The combination of the three vehicles with MF makes the formulated drug more active than MF alone against L. major promastigotes, however, only the combination with T904 increases the MF activity against intracellular amastigotes. With the aim of exploring gel-based formulations of the drug, the combination of MF and T1107 under gelation conditions has also been investigated.
000873827 536__ $$0G:(DE-HGF)POF3-6G4$$a6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623)$$cPOF3-623$$fPOF III$$x0
000873827 536__ $$0G:(DE-HGF)POF3-6G15$$a6G15 - FRM II / MLZ (POF3-6G15)$$cPOF3-6G15$$fPOF III$$x1
000873827 588__ $$aDataset connected to CrossRef
000873827 65027 $$0V:(DE-MLZ)SciArea-210$$2V:(DE-HGF)$$aSoft Condensed Matter$$x0
000873827 65017 $$0V:(DE-MLZ)GC-130-2016$$2V:(DE-HGF)$$aHealth and Life$$x0
000873827 693__ $$0EXP:(DE-MLZ)KWS2-20140101$$1EXP:(DE-MLZ)FRMII-20140101$$5EXP:(DE-MLZ)KWS2-20140101$$6EXP:(DE-MLZ)NL3ao-20140101$$aForschungs-Neutronenquelle Heinz Maier-Leibnitz $$eKWS-2: Small angle scattering diffractometer$$fNL3ao$$x0
000873827 7001_ $$0P:(DE-HGF)0$$aFernández-Rubio, Celia$$b1
000873827 7001_ $$0P:(DE-HGF)0$$aGonzález-Benito, Javier$$b2
000873827 7001_ $$0P:(DE-Juel1)171614$$aHouston, Judith E.$$b3
000873827 7001_ $$0P:(DE-Juel1)130905$$aRadulescu, Aurel$$b4
000873827 7001_ $$0P:(DE-HGF)0$$aNguewa, Paul$$b5$$eCorresponding author
000873827 7001_ $$0P:(DE-HGF)0$$aGonzález-Gaitano, Gustavo$$b6$$eCorresponding author
000873827 773__ $$0PERI:(DE-600)1484643-3$$a10.1016/j.ijpharm.2020.119057$$gVol. 578, p. 119057 -$$p119057$$tInternational journal of pharmaceutics$$v578$$x0378-5173$$y2020
000873827 8564_ $$uhttps://juser.fz-juelich.de/record/873827/files/Miltefosine-IJP-revised.pdf$$yPublished on 2020-01-25. Available in OpenAccess from 2021-01-25.
000873827 8564_ $$uhttps://juser.fz-juelich.de/record/873827/files/Miltefosine-IJP-revised.pdf?subformat=pdfa$$xpdfa$$yPublished on 2020-01-25. Available in OpenAccess from 2021-01-25.
000873827 909CO $$ooai:juser.fz-juelich.de:873827$$pdnbdelivery$$pVDB$$pVDB:MLZ$$pdriver$$popen_access$$popenaire
000873827 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)130905$$aForschungszentrum Jülich$$b4$$kFZJ
000873827 9131_ $$0G:(DE-HGF)POF3-623$$1G:(DE-HGF)POF3-620$$2G:(DE-HGF)POF3-600$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF3-6G4$$aDE-HGF$$bForschungsbereich Materie$$lVon Materie zu Materialien und Leben$$vFacility topic: Neutrons for Research on Condensed Matter$$x0
000873827 9131_ $$0G:(DE-HGF)POF3-6G15$$1G:(DE-HGF)POF3-6G0$$2G:(DE-HGF)POF3-600$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF3-6G15$$aDE-HGF$$bForschungsbereich Materie$$lGroßgeräte: Materie$$vFRM II / MLZ$$x1
000873827 9141_ $$y2020
000873827 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000873827 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000873827 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000873827 915__ $$0StatID:(DE-HGF)0530$$2StatID$$aEmbargoed OpenAccess
000873827 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bINT J PHARMACEUT : 2017
000873827 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000873827 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000873827 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000873827 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000873827 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000873827 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000873827 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000873827 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000873827 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000873827 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000873827 920__ $$lyes
000873827 9201_ $$0I:(DE-Juel1)JCNS-FRM-II-20110218$$kJCNS-FRM-II$$lJCNS-FRM-II$$x0
000873827 9201_ $$0I:(DE-Juel1)JCNS-1-20110106$$kJCNS-1$$lNeutronenstreuung$$x1
000873827 9201_ $$0I:(DE-588b)4597118-3$$kMLZ$$lHeinz Maier-Leibnitz Zentrum$$x2
000873827 980__ $$ajournal
000873827 980__ $$aVDB
000873827 980__ $$aUNRESTRICTED
000873827 980__ $$aI:(DE-Juel1)JCNS-FRM-II-20110218
000873827 980__ $$aI:(DE-Juel1)JCNS-1-20110106
000873827 980__ $$aI:(DE-588b)4597118-3
000873827 9801_ $$aFullTexts