Preclinical Pharmacokinetics and Biodistribution of Anticancer Dinuclear Palladium(II)-Spermine Complex (Pd(2)Spm) in Mice

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Vojtek, M (Author) Other; Goncalves Monteiro, S (Author) Other; Pinto, E (Author) Other; Kalivodova, S (Author) Other; Agostinho Almeida (Author) FFUP; Marques, MPM (Author) Other; de Carvalho, ALMB (Author) Other; Martins, CB (Author) Other; Mota Filipe, H (Author) Other; Ferreira, IMPLVO (Author) Other; Diniz, C (Author) FFUP

Journal

Title: Pharmaceuticals

Vol. 14

Pages: 1-16

ISSN: 1424-8247

Publisher: MDPI

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 8 Citations

Other information

Authenticus ID: P-00T-GV4

DOI: 10.3390/ph14020173

Abstract (EN): 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 (Pd(2)Spm), 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 Pd(2)Spm (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 Pd(2)Spm's cellular entry. This study reports, for the first time, the favorable pharmacokinetics and biodistribution of Pd(2)Spm, which may become a promising pharmacological agent for cancer treatment.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16