Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis
Hypothesis: Poloxamines are amphiphilic block copolymers that self-assemble forming polymeric micelles (PMs) and hydrogels. They have emerged as promising colloidal carriers for their potential in improving drug delivery and controlled release through their multi-responsive properties. Tetronic® 130...
| Autores: | , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Recursos: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/70035 |
| Acesso em linha: | https://hdl.handle.net/10171/70035 |
| Access Level: | acceso abierto |
| Palavra-chave: | Micelles Gels SANS Diffusion NMR Miltefosine Cyclodextrins Leishmania |
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Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasisDirany, Z. (Zeinab)|||/items/79322cf8-bf01-4566-93b1-85d29a99d3a7Smith, G.N. (Gregory N.)|||/items/c9f1a327-df6a-43bf-830d-16bf9ea2e691Aydillo-Miguel, C. (Carlos)|||/items/3ccc8e2e-211c-492b-9ec7-bf56ea016a8eNguewa, P.A. (Paul Alain)|||/items/27c2549c-5c98-42b4-b197-89f702d67c10González-Gaitano, G. (Gustavo)|||/items/28312e59-fbc3-4cbb-b753-a20a179cb545MicellesGelsSANSDiffusion NMRMiltefosineCyclodextrinsLeishmaniaHypothesis: Poloxamines are amphiphilic block copolymers that self-assemble forming polymeric micelles (PMs) and hydrogels. They have emerged as promising colloidal carriers for their potential in improving drug delivery and controlled release through their multi-responsive properties. Tetronic® 1307 (T1307) PMs and gels have been used herein as vehicles of host–guest complexes of cyclodextrins (CDs) and miltefosine (MF), an amphiphilic, anti-parasitic drug effective against leishmaniasis. Experiments: The association of MF to αCD, βCD, and HPβCD and the topology of the complexes have been fully characterized by NMR spectroscopy. Then, the structure of the complex-loaded PMs and hydrogels investigated using diffusion nuclear magnetic resonance (DOSY), small angle neutron scattering (SANS), and dynamic light scattering (DLS). The antileishmanial activity of the constructs was evaluated against Leishmania major promastigotes and amastigotes, as well as their cytotoxicity in macrophages. Findings: All the CDs investigated form highly stable inclusion complexes with MF in a 2CD:1MF stoichiometry that lead to considerable proportions of complexed drug at high dilution, the HPβCD providing the highest stability and compatibility with the poloxamine. The complex incorporates preferentially into the hydrophilic shell of the PMs, inducing the elongation of the aggregates and the dehydration of the micellar core, formed mainly by the PPO blocks. At high concentration of polymer and physiological temperature, the complex-loaded PMs pack in a BCC-type paracrystal network. The micellar formulations of the CD-complexed MF reduced the cytotoxicity of the drug, while enhancing its antileishmanial activity. This approach could improve the currently available treatments, facilitating the administration of MF at lower concentrations and achieving relevant therapeutic effects, not only through the intravenous route, but also as topical formulations through injectable thermogels for the treatment of the cutaneous and mucocutaneous forms of the disease.ElsevierDadun. Depósito Académico Digital Universidad de Navarra20242024-10-0120242024-01-0120242024-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/70035reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/700352026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis |
| title |
Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis |
| spellingShingle |
Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis Dirany, Z. (Zeinab)|||/items/79322cf8-bf01-4566-93b1-85d29a99d3a7 Micelles Gels SANS Diffusion NMR Miltefosine Cyclodextrins Leishmania |
| title_short |
Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis |
| title_full |
Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis |
| title_fullStr |
Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis |
| title_full_unstemmed |
Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis |
| title_sort |
Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis |
| dc.creator.none.fl_str_mv |
Dirany, Z. (Zeinab)|||/items/79322cf8-bf01-4566-93b1-85d29a99d3a7 Smith, G.N. (Gregory N.)|||/items/c9f1a327-df6a-43bf-830d-16bf9ea2e691 Aydillo-Miguel, C. (Carlos)|||/items/3ccc8e2e-211c-492b-9ec7-bf56ea016a8e Nguewa, P.A. (Paul Alain)|||/items/27c2549c-5c98-42b4-b197-89f702d67c10 González-Gaitano, G. (Gustavo)|||/items/28312e59-fbc3-4cbb-b753-a20a179cb545 |
| author |
Dirany, Z. (Zeinab)|||/items/79322cf8-bf01-4566-93b1-85d29a99d3a7 |
| author_facet |
Dirany, Z. (Zeinab)|||/items/79322cf8-bf01-4566-93b1-85d29a99d3a7 Smith, G.N. (Gregory N.)|||/items/c9f1a327-df6a-43bf-830d-16bf9ea2e691 Aydillo-Miguel, C. (Carlos)|||/items/3ccc8e2e-211c-492b-9ec7-bf56ea016a8e Nguewa, P.A. (Paul Alain)|||/items/27c2549c-5c98-42b4-b197-89f702d67c10 González-Gaitano, G. (Gustavo)|||/items/28312e59-fbc3-4cbb-b753-a20a179cb545 |
| author_role |
author |
| author2 |
Smith, G.N. (Gregory N.)|||/items/c9f1a327-df6a-43bf-830d-16bf9ea2e691 Aydillo-Miguel, C. (Carlos)|||/items/3ccc8e2e-211c-492b-9ec7-bf56ea016a8e Nguewa, P.A. (Paul Alain)|||/items/27c2549c-5c98-42b4-b197-89f702d67c10 González-Gaitano, G. (Gustavo)|||/items/28312e59-fbc3-4cbb-b753-a20a179cb545 |
| author2_role |
author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Micelles Gels SANS Diffusion NMR Miltefosine Cyclodextrins Leishmania |
| topic |
Micelles Gels SANS Diffusion NMR Miltefosine Cyclodextrins Leishmania |
| description |
Hypothesis: Poloxamines are amphiphilic block copolymers that self-assemble forming polymeric micelles (PMs) and hydrogels. They have emerged as promising colloidal carriers for their potential in improving drug delivery and controlled release through their multi-responsive properties. Tetronic® 1307 (T1307) PMs and gels have been used herein as vehicles of host–guest complexes of cyclodextrins (CDs) and miltefosine (MF), an amphiphilic, anti-parasitic drug effective against leishmaniasis. Experiments: The association of MF to αCD, βCD, and HPβCD and the topology of the complexes have been fully characterized by NMR spectroscopy. Then, the structure of the complex-loaded PMs and hydrogels investigated using diffusion nuclear magnetic resonance (DOSY), small angle neutron scattering (SANS), and dynamic light scattering (DLS). The antileishmanial activity of the constructs was evaluated against Leishmania major promastigotes and amastigotes, as well as their cytotoxicity in macrophages. Findings: All the CDs investigated form highly stable inclusion complexes with MF in a 2CD:1MF stoichiometry that lead to considerable proportions of complexed drug at high dilution, the HPβCD providing the highest stability and compatibility with the poloxamine. The complex incorporates preferentially into the hydrophilic shell of the PMs, inducing the elongation of the aggregates and the dehydration of the micellar core, formed mainly by the PPO blocks. At high concentration of polymer and physiological temperature, the complex-loaded PMs pack in a BCC-type paracrystal network. The micellar formulations of the CD-complexed MF reduced the cytotoxicity of the drug, while enhancing its antileishmanial activity. This approach could improve the currently available treatments, facilitating the administration of MF at lower concentrations and achieving relevant therapeutic effects, not only through the intravenous route, but also as topical formulations through injectable thermogels for the treatment of the cutaneous and mucocutaneous forms of the disease. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024-10-01 2024 2024-01-01 2024 2024-01-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/70035 |
| url |
https://hdl.handle.net/10171/70035 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
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Elsevier |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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15,81155 |