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

2021-02Journal article Open access
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dc.contributor.authorVojtek, Martin
dc.contributor.authorGonçalves-Monteiro, Salomé
dc.contributor.authorPinto, Edgar
dc.contributor.authorKalivodová, Sára
dc.contributor.authorAlmeida, Agostinho
dc.contributor.authorMarques, Maria P. M.
dc.contributor.authorBatista de Carvalho, Ana L. M.
dc.contributor.authorMartins, Clara B.
dc.contributor.authorMota-Filipe, Helder
dc.contributor.authorFerreira, Isabel M. P. L. V. O.
dc.contributor.authorDiniz, Carmen
dc.date.accessioned2021-04-07T08:23:44Z
dc.date.available2021-04-07T08:23:44Z
dc.date.issued2021-02
dc.description.abstractPalladium-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 treatmentpt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationVojtek, 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/ph14020173pt_PT
dc.identifier.doi10.3390/ph14020173pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.22/17801
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation.publisherversionhttps://www.mdpi.com/1424-8247/14/2/173pt_PT
dc.subjectPd(II)-based drugspt_PT
dc.subjectCisplatin ICP-MSpt_PT
dc.subjectMetal complexespt_PT
dc.subjectPolyaminespt_PT
dc.subjectCancerpt_PT
dc.subjectTissuept_PT
dc.subjectIn vivopt_PT
dc.titlePreclinical pharmacokinetics and biodistribution of anticancer dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in micept_PT
dc.typejournal article
dspace.entity.typePublication
person.familyNamePinto
person.givenNameEdgar
person.identifier.ciencia-id271F-B7DF-8FAB
person.identifier.orcid0000-0002-8021-4783
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationeaf9fc86-1a1c-437f-adee-d28040aa7f2f
relation.isAuthorOfPublication.latestForDiscoveryeaf9fc86-1a1c-437f-adee-d28040aa7f2f

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