Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites

In the present work, we study different physicochemical properties related to LADME processes of volasertib, a Polo-like kinase 1 inhibitor in advanced clinical trials. Firstly, the protonation equilibria, the extent of ionization at the physiological pH and pKa values of this drug are studied combi...

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Autores: Fernández-Sainz, J., Herrera-Ochoa, D., Pacheco-Liñán, P.J., Darder, Margarita, Albaladejo, J., Bravo, I., Garzón-Ruiz, A.
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2024
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/393409
Acesso em linha:http://hdl.handle.net/10261/393409
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85199070612&doi=10.1016%2fj.saa.2024.124823&partnerID=40&md5=a38137fff18eacabea13387c94bc795a
Access Level:Acceso aberto
Palavra-chave:Alginate
Montmorillonite
Bionanocomposite
Fluorescence spectroscopy in proteins
Human serum albumin
Volasertib
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spelling Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocompositesFernández-Sainz, J.Herrera-Ochoa, D.Pacheco-Liñán, P.J.Darder, MargaritaAlbaladejo, J.Bravo, I.Garzón-Ruiz, A.AlginateMontmorilloniteBionanocompositeFluorescence spectroscopy in proteinsHuman serum albuminVolasertibIn the present work, we study different physicochemical properties related to LADME processes of volasertib, a Polo-like kinase 1 inhibitor in advanced clinical trials. Firstly, the protonation equilibria, the extent of ionization at the physiological pH and pKa values of this drug are studied combining spectroscopic techniques and computational calculations. Secondly, the binding process of volasertib to the human serum albumin (HSA) protein is analyzed by fluorescence spectroscopy. We report a high binding constant to HSA (Ka = 4.10 × 106 M−1) and their pharmacokinetic implications are discussed accordingly. The negative enthalpy and entropy (ΔH0 = -54.49 kJ/mol; ΔS0 = -58.90 J K−1 mol−1) determined for the binding process suggests the implication of hydrogen bonds and van der Waals interactions in the formation of the HSA-volasertib complex. Additionally, volasertib is encapsulated in an alginate/montmorillonite bionanocomposite as a proof of concept for an oral delivery nanocarrier. The physical properties of that nanocomposite as well as volasertib delivery kinetics are analyzed. © 2024 The Author(s)This work is supported by ‘Universidad de Castilla-La Mancha’ through Projects 2022-GRIN-34143 and 2019-GRIN-27175 and by the ‘Junta de Comunidades de Castilla-La Mancha’ by the grants SBPLY/21/ 180501/000050. The authors also acknowledge support by the grants CPP2021-008597 and PID2020-117788RB-I00 funded by MCIN and Next Generation EU through Plan de Recuperaci´on, Transformaci´on y Resiliencia, and by grant PID2022-137889OB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”. J.P. L. thanks the ‘Junta de Comunidades de Castilla-La Mancha’ for his postdoctoral fellowship [2018/15132]. D.H. also thanks the ‘Universidad de Castilla-La Mancha’ for his predoctoral fellowship [2019/ 5964].Appendix A. Supplementary data Spectroscopic characterization; DFT calculations; Protein binding studies; Drug encapsulation and nanoparticle stabilityPeer reviewedElsevier BVConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/393409https://www.scopus.com/inward/record.uri?eid=2-s2.0-85199070612&doi=10.1016%2fj.saa.2024.124823&partnerID=40&md5=a38137fff18eacabea13387c94bc795areponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSpectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopyhttps://doi.org/10.1016/j.saa.2024.124823Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3934092026-05-22T06:33:51Z
dc.title.none.fl_str_mv Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites
title Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites
spellingShingle Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites
Fernández-Sainz, J.
Alginate
Montmorillonite
Bionanocomposite
Fluorescence spectroscopy in proteins
Human serum albumin
Volasertib
title_short Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites
title_full Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites
title_fullStr Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites
title_full_unstemmed Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites
title_sort Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites
dc.creator.none.fl_str_mv Fernández-Sainz, J.
Herrera-Ochoa, D.
Pacheco-Liñán, P.J.
Darder, Margarita
Albaladejo, J.
Bravo, I.
Garzón-Ruiz, A.
author Fernández-Sainz, J.
author_facet Fernández-Sainz, J.
Herrera-Ochoa, D.
Pacheco-Liñán, P.J.
Darder, Margarita
Albaladejo, J.
Bravo, I.
Garzón-Ruiz, A.
author_role author
author2 Herrera-Ochoa, D.
Pacheco-Liñán, P.J.
Darder, Margarita
Albaladejo, J.
Bravo, I.
Garzón-Ruiz, A.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Alginate
Montmorillonite
Bionanocomposite
Fluorescence spectroscopy in proteins
Human serum albumin
Volasertib
topic Alginate
Montmorillonite
Bionanocomposite
Fluorescence spectroscopy in proteins
Human serum albumin
Volasertib
description In the present work, we study different physicochemical properties related to LADME processes of volasertib, a Polo-like kinase 1 inhibitor in advanced clinical trials. Firstly, the protonation equilibria, the extent of ionization at the physiological pH and pKa values of this drug are studied combining spectroscopic techniques and computational calculations. Secondly, the binding process of volasertib to the human serum albumin (HSA) protein is analyzed by fluorescence spectroscopy. We report a high binding constant to HSA (Ka = 4.10 × 106 M−1) and their pharmacokinetic implications are discussed accordingly. The negative enthalpy and entropy (ΔH0 = -54.49 kJ/mol; ΔS0 = -58.90 J K−1 mol−1) determined for the binding process suggests the implication of hydrogen bonds and van der Waals interactions in the formation of the HSA-volasertib complex. Additionally, volasertib is encapsulated in an alginate/montmorillonite bionanocomposite as a proof of concept for an oral delivery nanocarrier. The physical properties of that nanocomposite as well as volasertib delivery kinetics are analyzed. © 2024 The Author(s)
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/393409
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85199070612&doi=10.1016%2fj.saa.2024.124823&partnerID=40&md5=a38137fff18eacabea13387c94bc795a
url http://hdl.handle.net/10261/393409
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85199070612&doi=10.1016%2fj.saa.2024.124823&partnerID=40&md5=a38137fff18eacabea13387c94bc795a
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy
https://doi.org/10.1016/j.saa.2024.124823
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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