Probing drug pharmacokinetics using neutron scattering techniques

Abstract

Quasi-elastic neutron scattering was applied to the study of human serum albumin metalation by anticancer drugs, with a specific focus on understanding the effects on the protein dynamics at the atomic scale. Two drugs were studied, a dinuclear Pd-complex and the clinical agent cisplatin. Both drugs prompted a decrease in the overall mobility of the protein, and this perturbation is closely associated with the protein's hydration layer. Opposite effects were detected for the Pt- and Pd-agents regarding the protein's local and internal dynamics. The influence of the Pd-compound at the nanosecond scale is particularly intriguing, as it reduced the observed backbone dynamics below 290 K. This enhanced knowledge on the drug's pharmacokinetics is expected to contribute to the design of improved anticancer agents (with lower toxicity and increased bioavailability at the target).