Anticancer activity and tissue distribution of platinum (II) complex with lignin-derived polymer of benzene-poly-carboxylic acids

Solovyev, Nikolay; Fedoros, Elena I.; Drobyshev, Evgenii; Ivanenko, N. B.; Pigarev, Sergey E.; Tyndyk, Margarita L.; Anisimov, Vladimir N.; Vilpan, Yury A.; Panchenko, Andrey

doi:10.1016/j.jtemb.2016.11.009

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…For platinum quantification, inductively coupled plasma mass spectrometry (ICP-MS) was used as described previously [ 47 , 48 ]. In brief, a microwave system UltraClave™ (Milestone, Sorisole, Italy) was used for sample digestion.…”

Section: Methodsmentioning

confidence: 99%

Modeling of Chemoperfusion vs. Intravenous Administration of Cisplatin in Wistar Rats: Adsorption and Tissue Distribution

et al. 2020

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Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an established form of locoregional chemotherapy of peritoneum tumors. However, its efficacy and safety status remain a controversy, partially, due to scarce data on pharmacokinetics and toxicity profile of drugs under HIPEC. In the current study, 24 female Wistar rats were randomly assigned to receive cisplatin as HIPEC (n = 12, 20 mg/kg) or intravenously (i.v., n = 9, 4 mg/kg). The subgroups of three animals were used for the initial, intermediate, and late phases of the pharmacokinetic assessment. The animals were sacrificed on days 1 and 5. Blood, liver, kidney, and ovaries were evaluated for platinum content. Histological and immunohistochemical evaluation was undertaken in the liver and kidney. A trend for higher blood plasma platinum levels was observed for HIPEC compared to i.v. Significantly lower (p < 0.001) relative platinum binding to the proteins was observed in HIPEC animals compared to the i.v. administration. A five-fold higher concentration of cisplatin in HIPEC resulted in a ca. 2.5-fold increase in total blood platinum and ca. two-fold increase in blood ultrafitrable platinum (“free” Pt). Immunohistochemistry revealed higher kidney and liver damage after i.v. administration of cisplatin compared to HIPEC, although a five-fold higher dose of cisplatin was applied in HIPEC. Together with relatively lower absorption to the systemic circulation in HIPEC, higher protein binding is probably the primary reason for lower observed toxicity in HIPEC animals.

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Section: Methodsmentioning

confidence: 99%

Modeling of Chemoperfusion vs. Intravenous Administration of Cisplatin in Wistar Rats: Adsorption and Tissue Distribution

et al. 2020

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“…Taking into account the dilution of initial plasma 1:2 per volume with PBS before dialysis, the following fractions of 'free' (unbound to macromolecules) platinum were calculated: 42.4 ± 5.0% and 11.8 ± 3.0 % (±SD) for the control buffer and plasma, respectively. Considering the macromolecular nature of the BP-C1 lignin-derived ligand (average molecular weight of 1500-2000 Da [7]), the contribution of binding to plasma proteins may be considered to be ca. 60% (61 ± 12%, ±2 SD, n = 24), since ca.…”

Section: Discussionmentioning

confidence: 99%

“…Platinum was quantified in plasma and plasma dialysates using inductively coupled plasma mass spectrometry (ICP-MS) after microwave digestion, as previously reported [7,23,25]. In brief, plasma or dialysate samples were digested with concentrated nitric acid in Teflon vessels and adjusted to the final volume of 25 mL in PFA volumetric flasks.…”

Section: Platinum Quantificationmentioning

confidence: 99%

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Protein Binding of a Novel Platinum-Based Anticancer Agent BP-C1 Containing a Lignin-Derived Polymeric Ligand

et al. 2021

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Platinum (Pt) antineoplastic agents remain indispensable for the treatment of oncological disease. Pt-based drugs are mainly used in the therapy of ovarian cancer and non-small-cell lung carcinoma. A novel platinum-containing antineoplastic agent BP-C1 is a complex of diamminoplatinum with an oxygen-donor polymeric ligand of benzene-polycarboxylic acids, isolated from natural lignin. The aim of the study was to investigate ex vivo protein binding of BP-C1. Protein binding of BP-C1 was tested using equilibrium dialysis. Pooled blood plasma was used in the study. Control solutions contained the same dosages of BP-C1 in PBS (pH 7.2). Plasma and control solutions were submitted to equilibrium dialysis across a vertical 8 kDa cut-off membrane for 4 h at 37 °C under gentle shaking. Platinum was quantified in dialysis and retained fractions using inductively coupled plasma mass spectrometry after microwave digestion. The dialysis system was tested and validated; this showed no protein saturation with platinum. A medium degree of binding of platinum to macromolecular species of ca. 60% was observed. The study showed the maintenance of a high fraction of free BP-C1 in the bloodstream, facilitating its pharmacological activity.

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Fourier transform ion cyclotron resonance mass spectrometry for the analysis of molecular composition and batch‐to‐batch consistency of plant‐derived polyphenolic ligands developed for biomedical application

Zherebker

Rukhovich

Kharybin

et al. 2020

Rapid Comm Mass Spectrometry

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RationaleComplex plant‐derived polyphenols are promising for biomedical application. Their high complexity prevents the use of conventional pharmacopoeia techniques to perform quality control. The goal of this study was to apply ultra‐high‐resolution mass spectrometry to evaluate the batch‐to‐batch consistency of the molecular composition of a polyphenolic ligand using appropriate statistical metrics.MethodsPolyphenols were obtained by hydrolyzed‐lignin oxidation. Manufacturing was performed under a range of reaction conditions: heating cycles, oxygen flows, purification. Direct‐injection Fourier transform ion cyclotron resonance mass spectrometry (DI FTICR‐MS) was applied to analyze reaction products. For pairwise comparison Jaccard and Tanimoto similarities calculations were proposed. In addition, principal component analysis (PCA) was applied for sample grouping based on the molecular class contributions.ResultsFTICR‐MS analysis revealed moderate Jaccard similarity of products synthesized under the same conditions, which shared about 50% of the formulae calculated in each sample. The intensity‐based Tanimoto index indicated high similarity of major components distribution of samples synthesized under standard conditions, while products obtained with variations in synthetic conditions were significantly different. PCA of molecular class contributions showed similar grouping with a high cumulative score.ConclusionsFTICR‐MS provides robust metrics for the examination of batch‐to‐batch consistency of synthetic polyphenol materials. This approach can be proposed for the analysis of reference samples and for development of complementary methods for quality control of medicinal agents based on various biologically active matrices.

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Anticancer activity and tissue distribution of platinum (II) complex with lignin-derived polymer of benzene-poly-carboxylic acids

Cited by 9 publications

References 31 publications

Modeling of Chemoperfusion vs. Intravenous Administration of Cisplatin in Wistar Rats: Adsorption and Tissue Distribution

Modeling of Chemoperfusion vs. Intravenous Administration of Cisplatin in Wistar Rats: Adsorption and Tissue Distribution

Protein Binding of a Novel Platinum-Based Anticancer Agent BP-C1 Containing a Lignin-Derived Polymeric Ligand

Fourier transform ion cyclotron resonance mass spectrometry for the analysis of molecular composition and batch‐to‐batch consistency of plant‐derived polyphenolic ligands developed for biomedical application

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