Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis

Serrano López, Dolores Remedios; Ballesteros Papantonakis, María De La Paloma; Bolas Fernández, Francisco; Fernandez-García, Raquel; Walsh, David; O'Connell, Peter; Passero, Luis Felipe; de Jesus, Jessica A.; Dalastra Laurenti, Marcia; Dea-Ayuela, Maria Auxiliadora; Lalatsa, Aikaterini; Healy, Anne Marie

Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis

The incidence of visceral leishmaniasis (VL) remains a significant health threat in endemic countries. Fixeddose combination (FDC) of amphotericin B (AmB) and miltefosine (MLT) is a promising strategy for treating VL, but the parenteral administration of AmB leads to severe side effects, limiting it...

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Autores:	Serrano López, Dolores Remedios, Ballesteros Papantonakis, María De La Paloma, Bolas Fernández, Francisco, Fernandez-García, Raquel, Walsh, David, O'Connell, Peter, Passero, Luis Felipe, de Jesus, Jessica A., Dalastra Laurenti, Marcia, Dea-Ayuela, Maria Auxiliadora, Lalatsa, Aikaterini, Healy, Anne Marie
Tipo de recurso:	artículo
Fecha de publicación:	2025
País:	España
Institución:	Universidad Complutense de Madrid (UCM)
Repositorio:	Docta Complutense
Idioma:	inglés
OAI Identifier:	oai:docta.ucm.es:20.500.14352/121063
Acceso en línea:	https://hdl.handle.net/20.500.14352/121063
Access Level:	acceso abierto
Palabra clave:	615.01/.03 615.03 615.2 615.06 oral delivery amphotericin B fixed-dose combination miltefosine coating visceral leishmaniasis Ciencias Biomédicas Farmacología (Farmacia) Medicamentos 3209 Farmacología 3209.90 Farmacología Experimental

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spelling	Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral LeishmaniasisSerrano López, Dolores RemediosBallesteros Papantonakis, María De La PalomaBolas Fernández, FranciscoFernandez-García, RaquelWalsh, DavidO'Connell, PeterPassero, Luis Felipede Jesus, Jessica A.Dalastra Laurenti, MarciaDea-Ayuela, Maria AuxiliadoraLalatsa, AikateriniHealy, Anne Marie615.01/.03615.03615.2615.06oral deliveryamphotericin Bfixed-dose combinationmiltefosinecoatingvisceral leishmaniasisCiencias BiomédicasFarmacología (Farmacia)Medicamentos3209 Farmacología3209.90 Farmacología ExperimentalThe incidence of visceral leishmaniasis (VL) remains a significant health threat in endemic countries. Fixeddose combination (FDC) of amphotericin B (AmB) and miltefosine (MLT) is a promising strategy for treating VL, but the parenteral administration of AmB leads to severe side effects, limiting its use in clinical practice. Here, we developed novel FDC granules combining AmB in the core with a MLT coating using wet granulation followed by the fluidized bed technology. The granules maintained the crystalline structure of AmB throughout manufacturing, achieving an AmB loading of ∼20%. The MLT coating layer effectively sustained AmB release from 3 to 24 h following Korsmeyer−Peppas kinetics. The formulation demonstrated remarkable stability, maintaining >90% drug content for over a year at both 4 °C and room temperature under desiccated conditions. In vivo efficacy studies in Leishmania infantum-infected hamsters showed 65−80% reduction in parasite burden in spleen and liver, respectively, suggesting potential as an oral alternative to current VL treatments. Uncoated and coated granules demonstrated comparable performance in key aspects, including in vivo efficacy and long-term stability.ACS PublicationsUniversidad Complutense de Madrid20252025-01-0120252025-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/121063reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-126310OA-I00open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1210632026-06-02T12:44:21Z
dc.title.none.fl_str_mv	Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis
title	Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis
spellingShingle	Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis Serrano López, Dolores Remedios 615.01/.03 615.03 615.2 615.06 oral delivery amphotericin B fixed-dose combination miltefosine coating visceral leishmaniasis Ciencias Biomédicas Farmacología (Farmacia) Medicamentos 3209 Farmacología 3209.90 Farmacología Experimental
title_short	Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis
title_full	Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis
title_fullStr	Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis
title_full_unstemmed	Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis
title_sort	Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis
dc.creator.none.fl_str_mv	Serrano López, Dolores Remedios Ballesteros Papantonakis, María De La Paloma Bolas Fernández, Francisco Fernandez-García, Raquel Walsh, David O'Connell, Peter Passero, Luis Felipe de Jesus, Jessica A. Dalastra Laurenti, Marcia Dea-Ayuela, Maria Auxiliadora Lalatsa, Aikaterini Healy, Anne Marie
author	Serrano López, Dolores Remedios
author_facet	Serrano López, Dolores Remedios Ballesteros Papantonakis, María De La Paloma Bolas Fernández, Francisco Fernandez-García, Raquel Walsh, David O'Connell, Peter Passero, Luis Felipe de Jesus, Jessica A. Dalastra Laurenti, Marcia Dea-Ayuela, Maria Auxiliadora Lalatsa, Aikaterini Healy, Anne Marie
author_role	author
author2	Ballesteros Papantonakis, María De La Paloma Bolas Fernández, Francisco Fernandez-García, Raquel Walsh, David O'Connell, Peter Passero, Luis Felipe de Jesus, Jessica A. Dalastra Laurenti, Marcia Dea-Ayuela, Maria Auxiliadora Lalatsa, Aikaterini Healy, Anne Marie
author2_role	author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Universidad Complutense de Madrid
dc.subject.none.fl_str_mv	615.01/.03 615.03 615.2 615.06 oral delivery amphotericin B fixed-dose combination miltefosine coating visceral leishmaniasis Ciencias Biomédicas Farmacología (Farmacia) Medicamentos 3209 Farmacología 3209.90 Farmacología Experimental
topic	615.01/.03 615.03 615.2 615.06 oral delivery amphotericin B fixed-dose combination miltefosine coating visceral leishmaniasis Ciencias Biomédicas Farmacología (Farmacia) Medicamentos 3209 Farmacología 3209.90 Farmacología Experimental
description	The incidence of visceral leishmaniasis (VL) remains a significant health threat in endemic countries. Fixeddose combination (FDC) of amphotericin B (AmB) and miltefosine (MLT) is a promising strategy for treating VL, but the parenteral administration of AmB leads to severe side effects, limiting its use in clinical practice. Here, we developed novel FDC granules combining AmB in the core with a MLT coating using wet granulation followed by the fluidized bed technology. The granules maintained the crystalline structure of AmB throughout manufacturing, achieving an AmB loading of ∼20%. The MLT coating layer effectively sustained AmB release from 3 to 24 h following Korsmeyer−Peppas kinetics. The formulation demonstrated remarkable stability, maintaining >90% drug content for over a year at both 4 °C and room temperature under desiccated conditions. In vivo efficacy studies in Leishmania infantum-infected hamsters showed 65−80% reduction in parasite burden in spleen and liver, respectively, suggesting potential as an oral alternative to current VL treatments. Uncoated and coated granules demonstrated comparable performance in key aspects, including in vivo efficacy and long-term stability.
publishDate	2025
dc.date.none.fl_str_mv	2025 2025-01-01 2025 2025-01-01
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/20.500.14352/121063
url	https://hdl.handle.net/20.500.14352/121063
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-126310OA-I00
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	ACS Publications
publisher.none.fl_str_mv	ACS Publications
dc.source.none.fl_str_mv	reponame:Docta Complutense instname:Universidad Complutense de Madrid (UCM)
instname_str	Universidad Complutense de Madrid (UCM)
reponame_str	Docta Complutense
collection	Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis

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