title: Comparative studies on drug binding to the purified and pharmaceutical-grade human serum albumins: Bridging between basic research and clinical applications of albumin.
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 Km and Vmax 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.
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Ashrafi-Kooshk
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Farangis
authors.initials: F
authors.lastname: Ebrahimi
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Ranjbar
authors.affiliation: Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.
authors.forename: Sirous
authors.initials: S
authors.lastname: Ghobadi
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Students' Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Moradi
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: rkhodarahmi@mbrc.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Khodarahmi
mesh_terms: D006801:Humans; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: D004364:Pharmaceutical Preparations; D012709:Serum Albumin
keywords: Albumin; Drug binding constant; Esterase activity; Infusion