期刊
APPLIED SCIENCES-BASEL
卷 11, 期 22, 页码 -出版社
MDPI
DOI: 10.3390/app112211008
关键词
protein binding; free platinum; anticancer drugs; lignin; equilibrium dialysis; inductively coupled plasma mass spectrometry; benzene-polycarboxylic acids; ex vivo studies
类别
资金
- Russian Science Foundation [20-15-00330]
- Russian Science Foundation [20-15-00330] Funding Source: Russian Science Foundation
The study investigated the ex vivo protein binding of the novel platinum-containing antineoplastic agent BP-C1. Results showed a medium degree of binding of platinum to macromolecular species of approximately 60%, indicating the maintenance of a high fraction of free BP-C1 in the bloodstream, facilitating its pharmacological activity.
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 & DEG;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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