RT Journal Article
T1 Targeted Oral Fixed-Dose Combination of Amphotericin B‑Miltefosine for Visceral Leishmaniasis
A1 Serrano López, Dolores Remedios
A1 Ballesteros Papantonakis, María De La Paloma
A1 Bolas Fernández, Francisco
A1 Fernandez-García, Raquel
A1 Walsh, David
A1 O'Connell, Peter
A1 Passero, Luis Felipe
A1 de Jesus, Jessica A.
A1 Dalastra Laurenti, Marcia
A1 Dea-Ayuela, Maria Auxiliadora
A1 Lalatsa, Aikaterini
A1 Healy, Anne Marie
AB 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.
PB ACS Publications
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/121063
UL https://hdl.handle.net/20.500.14352/121063
LA eng
NO Fernández-García R, Walsh D, O’Connell P, Passero LFD, De Jesus JA, Laurenti MD, et al. Targeted Oral Fixed-Dose Combination of Amphotericin B-Miltefosine for Visceral Leishmaniasis. Mol Pharmaceutics 2025;22:1437–48. https://doi.org/10.1021/acs.molpharmaceut.4c01133.
NO This work was funded by Banco de Santander-Universidad Complutense (project PR26/16-20355) and by the Iberoamerican Union of Universities (project ENF03/2017), awarded to F.B.-F. A.M.H. acknowledges a Science Foundation Ireland grant cofunded under the European Regional Development Fund (SFI/12/RC/22275_P2). This study has also been funded by the Ministry of Science and Innovation, Agencia Estatal de Investigación (award PID2021-126310OA-I00 to D.R.S.). Part of this study was funded by the São Paulo Research Foundation (FAPESP), LIM50-FMUSP, and the National Council for Scientific Development (CNPq) (grant number 2023/01641-1), awarded to L.F.D.P. and M.D.L.
NO Agencia Estatal de Investigación (España)
NO Universidad Complutense de Madrid
NO Banco de Santander (España)
NO Unión Iberoamericana de Universidades (UIU)
NO European Comission
NO Science Foundation Ireland
NO São Paulo Research Foundation (FAPESP)
NO National Council for Scientific Development (CNPq) (Brasil)
DS Docta Complutense
RD 14 jun 2025