Nicole Górniak, Wojciech Rogóż, Aleksandra Owczarzy, Małgorzata Maciążek-Jurczyk

Nanocalorimetric study of prednisone and prednisolone interaction with human serum albumin

2024-12-02

Subject of study. Prednisone (PRN) and its active form, prednisolone (PRL), are classified as synthetic glucocorticoids. They are used i.e. in acute and chronic inflammatory, autoimmune diseases and cancer therapy. Glucocorticoids can cause wide range of side effects. In order to reduce them, it is necessary to have detailed knowledge on their pharmacokinetics. There are available studies which describe the interaction between PRN, PRL and plasma proteins, especially human serum albumin (HSA), however, this type of data should be continuously improved and updated, especially using new research techniques.

The goal of the study. The aim of this study was to characterize the interaction between PRN and PRL with HSA using Nano Isothermal Titration Calorimetry (nanoITC, TA Instruments).

Materials and methods. Based on the validated methodology, both binding and thermodynamic parameters have been determined.

Results. The obtained association constant values for (HSA-PRN)complex and for (HSA-PRL)complex were Ka = (4.93 ± 2.33)∙105 [dm³/mol] and Ka = (2.79 ± 1.30)∙105 [dm³/mol], respectively. Simultaneously, the stoichiometry of (HSA-PRN)complex and (HSA-PRN)complex formation were n = 2.00 ± 0.17 and n = 2.14 ± 0.21. This phenomenon probably means that two molecules of PRN as well as PRL can interact with one molecule of HSA. The binding reaction of both PRN and PRL to HSA molecule had a spontaneous (ΔG < 0) and exothermic (ΔH < 0) character. Moreover, the negative values of both ΔH and ΔS in the case of (HSA-PRN)complex indicate that the complex was stabilized by hydrogen bonds and van der Waals forces. On the other hand, in the (PRL-HSA)complex, ionic bonds play an important role in complex stabilization (ΔH < 0, ΔS ~ 0).

Conclusions. Based on the presented data, it can be concluded that the studies with the use of nanoITC allowed to characterize the interaction in PRN-HSA and PRL-HSA complexes, and this technique can be a useful and comprehensive tool for the study of ligands-carrier proteins interaction.

Keywords: prednisone, prednisolone, albumin, calorimetry.

© Farm Pol, 2024, 80(7): 469–476