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Binding Kinetics of Cisplatin with Ion-exchange Resins

Abstract

Abstract

Objective: Localized chemotherapy can be more effective at treating cancers than traditional chemotherapy methods. Increased dosage leads to increased systemic toxicity, a critical issue that must be addressed. The ChemoFilter - a temporarily deployable, endovascular device - aims to extract chemotherapeutic agents from the bloodstream in order to reduce adverse side effects in other areas of the body. In this study, we report the binding effectiveness of ion-exchange resins with cisplatin, a commonly administered chemotherapeutic.

Materials and Methods: All experiments were conducted in vitro using cisplatin in distilled water and phosphate buffered saline. Ion-exchange resins (Dowex 50Wx2, Amberlite FPC22, Tulsion T-66, Amberlite IRC, Purolite S930/950) were tested in solution individually and the total amount of free cisplatin in solution was quantified using ultraviolet-visible spectroscopy and inductively coupled plasma mass spectroscopy.

Results: Quantification of cisplatin using UV-visible methods demonstrated that strong acid cation exchangers perform exceptionally well in saline solutions, removing over 90% of free cisplatin within one minute. The concentration of free cisplatin did not drop when reacted with strong cation exchangers in water. Weak acid cation exchangers and chelating resins also displayed no binding of cisplatin in PBS. Assessing the performance of the strong cation exchange resin, Dowex 50Wx2, using ICP-MS showed that ion exchange filtration was comparable in both water and PBS.

Conclusion: The current effectiveness of localized chemotherapy is limited by its corresponding increased systemic toxicity. The ChemoFilter seeks to mitigate the effects of chemotherapeutics on non-targeted areas of the body by extracting or inactivating the chemotherapy agents that pass through it. Our benchtop OPDA method of quantifying cisplatin in solution indicated that strong acid cation exchangers were exceptionally well-suited to the task. However, quantification using ICP-MS revealed that our previous UV-visible method of cisplatin quantification was not compatible with ion exchange resin studies and that these resins may not be very useful at fulfilling the ChemoFilter’s objective of removing cisplatin from solution.

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