Structural characterization by scattering and spectroscopic methods and biological evaluation of polymeric micelles of poloxamines and TPGS as nanocarriers for miltefosine delivery

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Show simple item record Puig-Rigall, Joan Fernandez-Rubio, Celia González Benito, Francisco Javier Houston, Judith E. Radulescu, Aurel Nguewa, Paul Gonzalez Gaitano, Gustavo 2021-06-22T07:43:48Z 2021-06-22T07:43:48Z 2020-03-30
dc.identifier.bibliographicCitation Puig-Rigall, J., Fernández-Rubio, C., González-Benito, J., Houston, J. E., Radulescu, A., Nguewa, P. & González-Gaitano, G. (2020). Structural characterization by scattering and spectroscopic methods and biological evaluation of polymeric micelles of poloxamines and TPGS as nanocarriers for miltefosine delivery. International Journal of Pharmaceutics, 578, 119057.
dc.identifier.issn 0378-5173
dc.description.abstract Miltefosine (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.
dc.description.sponsorship The authors gratefully acknowledge the financial support provided by MINECO (Project MAT2014-59116-C2), Obra Social La Caixa (LCF/PR/PR13/11080005), University Carlos III Strategic Action in Composites materials and interphases 2011/00287/002, Fundación Caja Navarra, Gobierno de Navarra-Salud (12/2017), Fundación Roviralta, Ubesol, Government of Navarre, Laser Ebro, Inversiones Garcilaso de la Vega and COST actions CA18217 and CA18218. JCNS is acknowledged for the access to the KWS-2 diffractometer at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany. J.P-R. also acknowledges the Asociación de Amigos de la Universidad de Navarra for his doctoral grant. This work benefited from the use of the SasView application, originally developed under NSF award DMR-0520547. Sasview contains code developed with funding from the European Union's Horizon 2020 research and innovation program under the SINE2020 project, grant agreement No 654000.
dc.format.extent 9
dc.language.iso eng
dc.publisher Elsevier
dc.rights © 2020 Elsevier B.V.
dc.rights Atribución-NoComercial-SinDerivadas 3.0 España
dc.subject.other Cytotoxicity
dc.subject.other Gels
dc.subject.other Micelles
dc.subject.other Miltefosine
dc.subject.other Poloxamine
dc.subject.other SANS
dc.subject.other Tetronic
dc.subject.other TPGS
dc.title Structural characterization by scattering and spectroscopic methods and biological evaluation of polymeric micelles of poloxamines and TPGS as nanocarriers for miltefosine delivery
dc.type article
dc.subject.eciencia Materiales
dc.subject.eciencia Química
dc.rights.accessRights openAccess
dc.relation.projectID Gobierno de España. MAT2014-59116-C2-1-R
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/654000/SINE2020
dc.type.version acceptedVersion
dc.identifier.publicationfirstpage 1
dc.identifier.publicationissue 119057
dc.identifier.publicationlastpage 9
dc.identifier.publicationtitle International Journal of Pharmaceutics
dc.identifier.publicationvolume 578
dc.identifier.uxxi AR/0000025613
dc.contributor.funder European Commission
dc.contributor.funder Ministerio de Economía y Competitividad (España)
dc.contributor.funder Universidad Carlos III de Madrid
dc.affiliation.dpto UC3M. Departamento de Ciencia e Ingeniería de Materiales e Ingeniería Química
dc.affiliation.grupoinv UC3M. Grupo de Investigación: Materiales compuestos poliméricos e interfases
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