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Article

Preclinical Pharmacokinetics and Biodistribution of Anticancer Dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in Mice

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LAQV/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
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LAQV/REQUIMTE, Laboratory of Bromatology and Hydrology, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
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Department of Environmental Health, School of Health, P.Porto, CISA/Research Center in Environment and Health, 4200-072 Porto, Portugal
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LAQV/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
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“Molecular Physical-Chemistry” R&D Unit, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal
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Department of Life Sciences, University of Coimbra, 3000-456 Coimbra, Portugal
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iMed.ULisboa, Faculty of Pharmacy, University of Lisbon, 1649-003 Lisbon, Portugal
*
Authors to whom correspondence should be addressed.
Academic Editor: Daniela Montesarchio
Pharmaceuticals 2021, 14(2), 173; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14020173
Received: 29 January 2021 / Revised: 13 February 2021 / Accepted: 17 February 2021 / Published: 23 February 2021
(This article belongs to the Special Issue Metal-Based Drugs: Updates and Perspectives)
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. View Full-Text
Keywords: Pd(II)-based drugs; cisplatin; ICP-MS; metal complexes; polyamines; cancer; tissue; in vivo Pd(II)-based drugs; cisplatin; ICP-MS; metal complexes; polyamines; cancer; tissue; in vivo
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MDPI and ACS Style

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. Preclinical Pharmacokinetics and Biodistribution of Anticancer Dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in Mice. Pharmaceuticals 2021, 14, 173. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14020173

AMA Style

Vojtek M, Gonçalves-Monteiro S, Pinto E, Kalivodová S, Almeida A, Marques MPM, Batista de Carvalho ALM, Martins CB, Mota-Filipe H, Ferreira IMPLVO, Diniz C. Preclinical Pharmacokinetics and Biodistribution of Anticancer Dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in Mice. Pharmaceuticals. 2021; 14(2):173. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14020173

Chicago/Turabian Style

Vojtek, Martin, Salomé Gonçalves-Monteiro, Edgar Pinto, Sára Kalivodová, Agostinho Almeida, Maria P.M. Marques, Ana L.M. Batista de Carvalho, Clara B. Martins, Helder Mota-Filipe, Isabel M.P.L.V.O. Ferreira, and Carmen Diniz. 2021. "Preclinical Pharmacokinetics and Biodistribution of Anticancer Dinuclear Palladium(II)-Spermine Complex (Pd2Spm) in Mice" Pharmaceuticals 14, no. 2: 173. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14020173

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