Spectroscopic study on volasertib: Highly stable complexes with albumin and encapsulation into alginate/montmorillonite bionanocomposites.

In the present work, we study different physicochemical properties related to LADME processes of volasertib, a Polo-like kinase 1 inhibitor in advanced clinical trials. Firstly, the protonation equilibria, the extent of ionization at the physiological pH and pK _a values of this drug are studied combining spectroscopic techniques and computational calculations. Secondly, the binding process of volasertib to the human serum albumin (HSA) protein is analyzed by fluorescence spectroscopy. We report a high binding constant to HSA (K _a  = 4.10 × 10 ⁶ M ^-1 ) and their pharmacokinetic implications are discussed accordingly. The negative enthalpy and entropy (ΔH ⁰  = -54.49 kJ/mol; ΔS ⁰  = -58.90 J K ^-1 mol ^-1 ) determined for the binding process suggests the implication of hydrogen bonds and van der Waals interactions in the formation of the HSA-volasertib complex. Additionally, volasertib is encapsulated in an alginate/montmorillonite bionanocomposite as a proof of concept for an oral delivery nanocarrier. The physical properties of that nanocomposite as well as volasertib delivery kinetics are analyzed.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andres Garzon Ruiz reports financial support was provided by Universidad de Castilla-La Mancha. Ivan Bravo reports financial support was provided by Junta de Comunidades de Castilla-La Mancha. Andres Garzon Ruiz reports financial support was provided by Spain Ministry of Science and Innovation. Margarita Darder reports financial support was provided by Spain Ministry of Science and Innovation. Pedro J. Pacheco Linan reports financial support was provided by Junta de Comunidades de Castilla-La Mancha. Diego Herrera reports financial support was provided by University of Castilla-La Mancha. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)