Affiliation:
1. Department of Pharmacy and Ecological Chemistry, Institute of Chemistry, University of Opole, Oleska 48, 45-052
Opole, Poland
Abstract
Background:
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are one of the most
commonly used groups of medicinal compounds in the world. The wide access to NSAIDs and the
various ways of storing them due to their easy accessibility often entail the problem with the stability and durability resulting from the exposure of drugs to external factors.
The aim of the research was to evaluate in vitro the mechanism of competition between ibuprofen
(IBU) and its degradation products, i.e., 4'-isobutylacetophenone (IBAP) and (2RS)-2-(4-
formylphenyl)propionic acid (FPPA) during transport in a complex with fatted (HSA) and defatted
(dHSA) human serum albumin.
Methods:
The research was carried out using spectroscopic techniques, such as spectrophotometry, infrared spectroscopy and nuclear magnetic resonance spectroscopy
Results:
The comprehensive application of spectroscopic techniques allowed, among others, for
the determination of the binding constant, the number of classes of binding sites and the cooperativeness constant of the analyzed systems IBU-(d)HSA, IBU-(d)HSA-FPPA, IBU-(d)HSA-IBAP;
the determination of the effect of ibuprofen and its degradation products on the secondary structure of albumin; identification and assessment of interactions between ligand and albumin; assessment of the impact of the presence of fatty acids in the structure of albumin and the measurement temperature on the binding of IBU, IBAP and FPPA to (d)HSA.
Conclusion:
The conducted research allowed us to conclude that the presence of ibuprofen degradation products and the increase in their concentration significantly affect the formation of the
IBU-albumin complex and thus, the value of the association constant of the drug, changing the
concentration of its free fraction in the blood plasma. It was also found that the presence of an ibuprofen degradation product in a complex with albumin affects its secondary structure.
Publisher
Bentham Science Publishers Ltd.