Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in mice

Detalhes bibliográficos
Autor(a) principal: Vojtek, Martin
Data de Publicação: 2021
Outros Autores: Gonçalves-Monteiro, Salomé, Pinto, Edgar, Kalivodová, Sára, Almeida, Agostinho, Marques, Maria P. M., Batista de Carvalho, Ana L. M., Martins, Clara B., Mota-Filipe, Helder, Ferreira, Isabel M. P. L. V. O., Diniz, Carmen
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.22/17801
Resumo: Palladium-based compounds are regarded as potential analogs to platinum anticancer drugs with improved properties. The present study assessed the pharmacokinetics and biodistribution of a dinuclear palladium(II)-spermine chelate (Pd2Spm), which has previously been shown to possess promising in vitro activity against several therapy-resistant cancers. Using inductively coupled plasma-mass spectrometry, the kinetic profiles of palladium/platinum in serum, serum ultrafiltrate and tissues (kidney, liver, brain, heart, lungs, ovaries, adipose tissue and mammary glands) were studied in healthy female Balb/c mice after a single intraperitoneal bolus injection of Pd2Spm (3 mg/kg bw) or cisplatin (3.5 mg/kg bw) between 0.5 and 48 h post-injection. Palladium in serum exhibited biphasic kinetics with a terminal half-life of 20.7 h, while the free palladium in serum ultrafiltrate showed a higher terminal half-life than platinum (35.5 versus 31.5 h). Palladium was distributed throughout most of the tissues except for the brain, with the highest values in the kidney, followed by the liver, lungs, ovaries, adipose tissue and mammary glands. The in vitro cellular accumulation was also evaluated in breast cancer cells, evidencing a passive diffusion as a mechanism of Pd2Spm’s cellular entry. This study reports, for the first time, the favorable pharmacokinetics and biodistribution of Pd2Spm, which may become a promising pharmacological agent for cancer treatment
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spelling Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in micePd(II)-based drugsCisplatin ICP-MSMetal complexesPolyaminesCancerTissueIn vivoPalladium-based compounds are regarded as potential analogs to platinum anticancer drugs with improved properties. The present study assessed the pharmacokinetics and biodistribution of a dinuclear palladium(II)-spermine chelate (Pd2Spm), which has previously been shown to possess promising in vitro activity against several therapy-resistant cancers. Using inductively coupled plasma-mass spectrometry, the kinetic profiles of palladium/platinum in serum, serum ultrafiltrate and tissues (kidney, liver, brain, heart, lungs, ovaries, adipose tissue and mammary glands) were studied in healthy female Balb/c mice after a single intraperitoneal bolus injection of Pd2Spm (3 mg/kg bw) or cisplatin (3.5 mg/kg bw) between 0.5 and 48 h post-injection. Palladium in serum exhibited biphasic kinetics with a terminal half-life of 20.7 h, while the free palladium in serum ultrafiltrate showed a higher terminal half-life than platinum (35.5 versus 31.5 h). Palladium was distributed throughout most of the tissues except for the brain, with the highest values in the kidney, followed by the liver, lungs, ovaries, adipose tissue and mammary glands. The in vitro cellular accumulation was also evaluated in breast cancer cells, evidencing a passive diffusion as a mechanism of Pd2Spm’s cellular entry. This study reports, for the first time, the favorable pharmacokinetics and biodistribution of Pd2Spm, which may become a promising pharmacological agent for cancer treatmentMDPIRepositório Científico do Instituto Politécnico do PortoVojtek, MartinGonçalves-Monteiro, SaloméPinto, EdgarKalivodová, SáraAlmeida, AgostinhoMarques, Maria P. M.Batista de Carvalho, Ana L. M.Martins, Clara B.Mota-Filipe, HelderFerreira, Isabel M. P. L. V. O.Diniz, Carmen2021-04-07T08:23:44Z2021-022021-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.22/17801engVojtek, M., Gonçalves-Monteiro, S., Pinto, E., Kalivodová, S., Almeida, A., Marques, M. P. M., Batista de Carvalho, A. L. M., Martins, C. B., Mota-Filipe, H., Ferreira, I. M. P. L. V. O., & Diniz, C. (2021). Preclinical Pharmacokinetics and Biodistribution of Anticancer Dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in Mice. Pharmaceuticals, 14(2). https://doi.org/10.3390/ph1402017310.3390/ph14020173info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-13T13:08:57Zoai:recipp.ipp.pt:10400.22/17801Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:37:25.276542Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in mice
title Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in mice
spellingShingle Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in mice
Vojtek, Martin
Pd(II)-based drugs
Cisplatin ICP-MS
Metal complexes
Polyamines
Cancer
Tissue
In vivo
title_short Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in mice
title_full Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in mice
title_fullStr Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in mice
title_full_unstemmed Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in mice
title_sort Preclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in mice
author Vojtek, Martin
author_facet Vojtek, Martin
Gonçalves-Monteiro, Salomé
Pinto, Edgar
Kalivodová, Sára
Almeida, Agostinho
Marques, Maria P. M.
Batista de Carvalho, Ana L. M.
Martins, Clara B.
Mota-Filipe, Helder
Ferreira, Isabel M. P. L. V. O.
Diniz, Carmen
author_role author
author2 Gonçalves-Monteiro, Salomé
Pinto, Edgar
Kalivodová, Sára
Almeida, Agostinho
Marques, Maria P. M.
Batista de Carvalho, Ana L. M.
Martins, Clara B.
Mota-Filipe, Helder
Ferreira, Isabel M. P. L. V. O.
Diniz, Carmen
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Politécnico do Porto
dc.contributor.author.fl_str_mv Vojtek, Martin
Gonçalves-Monteiro, Salomé
Pinto, Edgar
Kalivodová, Sára
Almeida, Agostinho
Marques, Maria P. M.
Batista de Carvalho, Ana L. M.
Martins, Clara B.
Mota-Filipe, Helder
Ferreira, Isabel M. P. L. V. O.
Diniz, Carmen
dc.subject.por.fl_str_mv Pd(II)-based drugs
Cisplatin ICP-MS
Metal complexes
Polyamines
Cancer
Tissue
In vivo
topic Pd(II)-based drugs
Cisplatin ICP-MS
Metal complexes
Polyamines
Cancer
Tissue
In vivo
description Palladium-based compounds are regarded as potential analogs to platinum anticancer drugs with improved properties. The present study assessed the pharmacokinetics and biodistribution of a dinuclear palladium(II)-spermine chelate (Pd2Spm), which has previously been shown to possess promising in vitro activity against several therapy-resistant cancers. Using inductively coupled plasma-mass spectrometry, the kinetic profiles of palladium/platinum in serum, serum ultrafiltrate and tissues (kidney, liver, brain, heart, lungs, ovaries, adipose tissue and mammary glands) were studied in healthy female Balb/c mice after a single intraperitoneal bolus injection of Pd2Spm (3 mg/kg bw) or cisplatin (3.5 mg/kg bw) between 0.5 and 48 h post-injection. Palladium in serum exhibited biphasic kinetics with a terminal half-life of 20.7 h, while the free palladium in serum ultrafiltrate showed a higher terminal half-life than platinum (35.5 versus 31.5 h). Palladium was distributed throughout most of the tissues except for the brain, with the highest values in the kidney, followed by the liver, lungs, ovaries, adipose tissue and mammary glands. The in vitro cellular accumulation was also evaluated in breast cancer cells, evidencing a passive diffusion as a mechanism of Pd2Spm’s cellular entry. This study reports, for the first time, the favorable pharmacokinetics and biodistribution of Pd2Spm, which may become a promising pharmacological agent for cancer treatment
publishDate 2021
dc.date.none.fl_str_mv 2021-04-07T08:23:44Z
2021-02
2021-02-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.22/17801
url http://hdl.handle.net/10400.22/17801
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Vojtek, M., Gonçalves-Monteiro, S., Pinto, E., Kalivodová, S., Almeida, A., Marques, M. P. M., Batista de Carvalho, A. L. M., Martins, C. B., Mota-Filipe, H., Ferreira, I. M. P. L. V. O., & Diniz, C. (2021). Preclinical Pharmacokinetics and Biodistribution of Anticancer Dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in Mice. Pharmaceuticals, 14(2). https://doi.org/10.3390/ph14020173
10.3390/ph14020173
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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