Comparative studies on drug binding to the purified and pharmaceutical-grade human serum albumins: Bridging between basic research and clinical applications of albumin. Issue 5 (September 2015)

• Record Type: Journal Article
• Authors: Ashrafi-Kooshk, Mohammad Reza; Ebrahimi, Farangis; Ranjbar, Samira; Ghobadi, Sirous; Moradi, Nastaran; Khodarahmi, Reza
• Is Part Of: Biologicals. Volume 43:Issue 5(2015:Sep.)
• Page Start: 333
• Page End: 343
• Publication Date: 2015-09
• Subjects: Albumin -- Infusion -- Drug binding constant -- Esterase activity; Biological products -- Standards -- Periodicals; Biological Products -- Periodicals; Biological Products -- standards -- Periodicals; Produits biologiques -- Normes -- Périodiques; Biological products -- Standards; Periodicals; 615.37
• DOI: 10.1016/j.biologicals.2015.07.003
• Languages: English
• ISSNs: 1045-1056

Abstract

Abstract: Human serum albumin (HSA), the most abundant protein in blood plasma, is a monomeric multidomain protein that possesses an extraordinary capacity for binding, so that serves as a circulating depot for endogenous and exogenous compounds. During the heat sterilization process, the structure of pharmaceutical-grade HSA may change and some of its activities may be lost. In this study, to provide deeper insight on this issue, we investigated drug-binding and some physicochemical properties of purified albumin (PA) and pharmaceutical-grade albumin (PGA) using two known drugs (indomethacin and ibuprofen). PGA displayed significantly lower drug binding capacity compared to PA. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between the drugs and the proteins are different from each other. Surface hydrophobicity as well as the stability of PGA decreased compared to PA, also surface hydrophobicity of PA and PGA increased upon drugs binding. Also, kinetic analysis of pseudo-esterase activities indicated that K m and V max parameters for PGA enzymatic activity are more and less than those of PA, respectively. This in vitro study demonstrates that the specific drug binding of PGA is significantly reduced. Such studies can act as connecting bridge between basic research discoveries and clinical applications. Highlights: PGA displayed significantly lower drug binding capacity compared to PA. Intermolecular interactions between the drugs and the proteins are different from each other. Surface hydrophobicity as well as the stability of PGA decreased compared to PA. Surface hydrophobicity of PA and PGA increased upon drugs binding. K m and V max parameters for PGA enzymatic activity are more and less than those of PA, respectively.