title: Imidazolium ionic liquids as solvents of pharmaceuticals: influence on HSA binding and partition coefficient of nimesulide.
abstract: In this work, the influence of imidazolium ionic liquids (ILs) on bio-chemical parameters that influence the in vivo behavior of nimesulide was evaluated. In this context, the binding of nimesulide to human serum albumin (HSA), in IL media, was studied. In parallel, the evaluation of the interaction of drug-IL systems, with micelles of hexadecylphosphocholine (HDPC), enabled the calculation of partition coefficients (K(p)). Both assays were performed in buffered media in the absence and in the presence of emim [BF(4)], emim [Ms] and emim [TfMs] 1%. Even though there was an increase of the dissociation constant (K(d)) in IL media, nimesulide still binds to HSA by means of strong interactions. The thermodynamic analysis indicates that the interaction is spontaneous for all the tested systems. Moreover, the studied systems exhibited properties that are favorable to the interaction of the drug with biological membranes, with K(p) values 2.5-3.5 higher than in aqueous environment. The studied nimesulide-IL systems presented promising characteristics regarding the absorption and distribution of the drug in vivo, so that the studied solvents seem to be good options for drug delivery.
authors.affiliation: REQUIMTE, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 4050-313 Porto, Portugal.
authors.forename: Ana M O
authors.initials: AM
authors.lastname: Azevedo
authors.forename: Diogo M G
authors.initials: DM
authors.lastname: Ribeiro
authors.forename: Paula C A G
authors.initials: PC
authors.lastname: Pinto
authors.forename: Marlene
authors.initials: M
authors.lastname: Lúcio
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
authors.forename: M Lúcia M F S
authors.initials: ML
authors.lastname: Saraiva
mesh_terms: D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000737:chemistry*; D052578:Ionic Liquids / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry; D008954:Models, Biological; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D052578:Ionic Liquids; D008563:Membrane Lipids; D008565:Membrane Proteins; D012709:Serum Albumin; D012997:Solvents; D013449:Sulfonamides; D010767:Phosphorylcholine; C039128:miltefosine; C012655:nimesulide