Displacement of Drugs from Human Serum Albumin: From Molecular Interactions to Clinical Significance

Rimac, Hrvoje; Debeljak, Željko; Bojić, Mirza; Miller, Larisa

doi:10.2174/0929867324666170202152134

Cited by 37 publications

(30 citation statements)

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“…The second is the "protein corona," whereby proteins form a corona around NPs. The combination of different NPs cannot be separated from electrostatic interaction, van der Waals force, hydrogen bond, and hydrophobic interaction [49].…”

Section: Discussionmentioning

confidence: 99%

Interaction of Mitoxantrone-Loaded Cholesterol Modified Pullulan Nanoparticles with Human Serum Albumin and Effect on Drug Release

Yuan

Guo

Zhong

et al. 2019

Journal of Nanomaterials

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To clarify nanoparticle-protein interaction and their action characteristics, the interactions between MTO-CHP NPs and human serum albumin (HSA) were studied by isothermal titration calorimetry (ITC), fluorescence spectroscopy, dynamic light scattering (DLS), and circular dichroism spectroscopy (CD). Hydrophobically modified pullulan (CHP) nanoparticles (NPs) loaded with mitoxantrone (MTO) were prepared (MTO-CHP NPs) with size 166.9 nm. The spherical shape was verified by transmission electron microscopy (TEM). The ITC results demonstrated an interaction between MTO-CHP NPs mainly by hydrophobic interaction force, electrostatic force, and hydrogen bonding. The mean binding constant KA was 0.832×104 M−1 and mean HSA coverage 0.939±0.302. MTO-CHP NPs could quench the fluorescence intensity of HSA, which gradually decreased to be balanced in 9 h and indicated the completion of the complexation. The size and zeta potential changes of the combined particle were dynamically detected with DLS at 0, 3, 6, 9, 12, 15, and 18 h. When the reaction was completed at 9 h, the particle size and potential remained stable, accompanied by a size change from 89.91 to about 145 nm and potential change from -15 to -3 mV, respectively. The results of CD measurement showed that the change in ellipticity of HSA at 208 nm was similar to the fluorescence spectra and DLS measurements with MTO-CHP NPs combined with HSA. At the beginning of the reaction, the proportion of α-helix was 52.3% to 43.7%, which decreased by 39.1% at compound stabilization. The release of MTO from MTO-CHP NPs at pH=5.6 was significantly accelerated, whereas that of MTO from HSA-MTO-CHP NPs was significantly reduced, and the drug release was significantly slowed down even under acidic conditions, which indicates the beneficial effect of HSA on the persistence and stability of the HSA-MTO-CHP NP compound.

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Section: Discussionmentioning

confidence: 99%

Interaction of Mitoxantrone-Loaded Cholesterol Modified Pullulan Nanoparticles with Human Serum Albumin and Effect on Drug Release

Yuan

Guo

Zhong

et al. 2019

Journal of Nanomaterials

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“…It is known that several drugs can be detected in plasma as serum albumin-bound conjugates, as these are the most abundant multifunctional transport proteins. 12,13 The interaction with these plasma proteins can lead to changes in absorption, distribution, metabolism, and excretion properties. Moreover, it can lead to attenuation of drug potency, according to the free drug principle.…”

Section: Introductionmentioning

confidence: 99%

Tianeptine Esters Derivatives: A Study of Protein-Drug Interaction Performed by Fluorescence Quenching and Molecular Docking

Soares

Ceschi

Franceschini

et al. 2019

J. Braz. Chem. Soc.

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The nature of binding between bovine serum albumin (BSA) and the antidepressant tianeptine and a new series of esters derivatives were studied in this paper. The interactions with BSA were investigated by UV-Vis and fluorescence spectroscopy at three different temperatures. The fluorescence quenching experiments showed that BSA interactions with tianeptine could be dynamic while to its esters a static mechanism was observed. The results showed that tianeptine quenches the intrinsic fluorescence of BSA more efficiently than its esters due to the presence of the free acid portion. The number of binding sites determined by fluorescence spectroscopy is approximately equal to 1 indicating that there is one binding site between BSA tianeptine esters, but the presence of a second interaction site for tianeptine at higher temperatures could be not ruled out. Molecular docking calculations point out a strong affinity of tianeptine and its esters to the site IIA of protein, supporting the hypothesis of a static quenching mechanism.

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“…In the present study, warfarin was used as the reference compound to map binding at site I. However, it is well known that a wide number of drugs interact with albumin at the same site with similar affinity [13,15].…”

Section: Protein Fluorescencementioning

confidence: 99%

“…The transport and regulation functions of these proteins are possible by the numerous binding sites present in their structure; the regulation of site affinity for the ligand can be modulated by pH-dependent conformational microtransitions, competitive displacements and uncompetitive interactions. Of the numerous binding sites, Sudlow I (in the subdomain IIa) and Sudlow II (in the subdomain IIIa) are studied in detail as high-affinity sites (K A~1 0 4 -10 6 L mol −1 ) of interest for the transport of numerous drugs and bioactive molecules [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Interaction of the Coffee Diterpenes Cafestol and 16-O-Methyl-Cafestol Palmitates with Serum Albumins

Berti

Navarini²,

Guercia³

et al. 2020

IJMS

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The main coffee diterpenes cafestol, kahweol, and 16-O-methylcafestol, present in the bean lipid fraction, are mostly esterified with fatty acids. They are believed to induce dyslipidaemia and hypercholesterolemia when taken with certain types of coffee brews. The study of their binding to serum albumins could help explain their interactions with biologically active xenobiotics. We investigated the interactions occurring between cafestol and 16-O-methylcafestol palmitates with Bovine Serum Albumin (BSA), Human Serum Albumin (HSA), and Fatty Free Human Serum Albumin (ffHSA) by means of circular dichroism and fluorimetry. Circular Dichroism (CD) revealed a slight change (up to 3%) in the secondary structure of fatty-free human albumin in the presence of the diterpene esters, suggesting that the aliphatic chain of the palmitate partly occupies one of the fatty acid sites of the protein. A warfarin displacement experiment was performed to identify the binding site, which is probably close but not coincident with Sudlow site I, as the affinity for warfarin is enhanced. Fluorescence quenching titrations revealed a complex behaviour, with Stern–Volmer constants in the order of 103–104 Lmol−1. A model of the HSA-warfarin-cafestol palmitate complex was obtained by docking, and the most favourable solution was found with the terpene palmitate chain inside the FA4 fatty acid site and the cafestol moiety fronting warfarin at the interface with site I.

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Displacement of Drugs from Human Serum Albumin: From Molecular Interactions to Clinical Significance

Abstract: In present paper we review drug interactions with potential for displacement from HSA, situations in which they are likely to occur and their clinical significance. We also offer guidelines in designing drugs with decreased binding to HSA.

Cited by 37 publications

References 0 publications

Interaction of Mitoxantrone-Loaded Cholesterol Modified Pullulan Nanoparticles with Human Serum Albumin and Effect on Drug Release

Interaction of Mitoxantrone-Loaded Cholesterol Modified Pullulan Nanoparticles with Human Serum Albumin and Effect on Drug Release

Tianeptine Esters Derivatives: A Study of Protein-Drug Interaction Performed by Fluorescence Quenching and Molecular Docking

Interaction of the Coffee Diterpenes Cafestol and 16-O-Methyl-Cafestol Palmitates with Serum Albumins

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