Interaction of platinum agents, cisplatin, carboplatin and oxaliplatin against albumin in vivo rats and in vitro study using inductively coupled plasma‐mass spectrometory

Abstract

The protein binding rates (PBR) of platinum‐containing agents cisplatin (CDDP), carboplatin (CBDCA) and oxaliplatin (L‐OHP) have been reported as 98%, 25–50% and 98%, respectively. To investigate the protein‐binding properties of albumin with cisplatin, carboplatin and oxaliplatin, inductively coupled plasma mass spectrometry (ICP‐MS) was used to measure their plasma concentration in rats over time. The study also examined the effects of cisplatin, carboplatin and oxaliplatin‐binding on albumin in vitro, using CD spectrometry and native‐polyacrylamide gel electrophoresis (native PAGE). The ratios of PBR to irreversible PBR, of cisplatin and oxaliplatin were 98%:98% and 90%:87%, respectively, indicating a higher affinity for irreversible binding with albumin. That of carboplatin was 25%:10%, indicating 60–70% reversible binding with albumin. The plasma protein binding rate concentrations of cisplatin, carboplatin and oxaliplatin after in vivo administration were 96%, 15% and 80%, respectively. The CD spectrometry of albumin was unaffected by cisplatin, carboplatin and oxaliplatin binding. Though similar protein binding rates were observed with oxaliplatin and cisplatin, oxaliplatin had a higher mobility rate during PAGE. It was confirmed that the binding of cisplatin and oxaliplatin with albumin affected its electric charge but not the structure. In conclusion, cisplatin and oxaliplatin bind irreversibly with albumin in plasma and may irreversibly interact with tissue protein and/or DNA. The difficulties involved with predicting the tissue concentrations of cisplatin and oxaliplatin from their plasma concentration inhibits their therapeutic drug monitoring. On the contrary, carboplatin, like some generic drugs, reversibly binds to plasma proteins. It is, therefore, possible to conduct therapeutic drug monitoring for carboplatin.

A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis

“…The pharmacokinetics results highlighted a very slow decrease of the plasma concentration of CDDP and OXA over time. This behavior can be related to the binding of the two platin compounds to the plasma albumin [37,38].…”

A chemical perspective on the clinical use of platinum-based anticancer drugs

“…44 Similar figures are also observed for oxaliplatin (up to 98% protein bound) but protein binding by carboplatin is significantly lower at 25–50%. 45 Human serum albumin (HSA) is the most abundant protein in blood serum at a concentration of 35–50 mg mL −1 (0.53–0.75 mM) and is a significant contributor to the maintenance of blood serum osmotic balance. In addition to providing osmotic pressure, HSA is also used by the body to transport metal ions ( e.g.…”

Comprehensive and systematic characterization of multi-functionalized cisplatin nano-conjugate: from the chemistry and proteomic biocompatibility to the animal model

“…The functional enrichment of the detected proteins provide a view of the type of protein binding in this case, where mostly of them are related to blood functions (coagulation, would healing…). Knowing that these factors are in the protein contain of FBS, it is understandable that the presence of Pt displaces these proteins towards the soft-corona, as these proteins interact with more affinity with the metal [ 25 , 26 ] and do not reach to interact with the IONP surface (Additional file 1 : Table S1). Finally, human protein corona reveals the largest differences between identified proteins at hard and soft coronas (Fig.…”