title: Supramolecular aggregates of oligosaccharides with co-solvents in ternary systems for the solubilizing approach of triamcinolone.
abstract: A second compound is generally associated with oligosaccharides as a strategy to maximize the solubilizing effect for nonpolar compounds. This study elucidated the role and the mechanism whereby liquid compounds interact in these supramolecular aggregates in the solubilization of triamcinolone. Three different oligosaccharides (beta-cyclodextrin, 2-hydroxipropil-beta-cyclodextrin, and randomly methylated beta-cyclodextrin) and two potent co-solvents (triethanolamine and N-methyl pyrrolidone) were carefully evaluated by using three distinct experimental approaches. Incredibly stable complexes were formed with cyclodextrins (CDs). The structure of the complexes was elucidated by magnetic resonance spectra 2D-ROESY. The interactions of the protons of ring "A" of the drug with H(3) and H(5) protons of the CD cavity observed in the binary complexes remained in both ternary complexes. Unlike the observed ternary associations with triethanolamine, N-methyl pyrrolidone competed with the triamcinolone CD cavity and considerably decreased the stability of the complex and the solubility of the drug. The molecular dynamics (MD) and quantum mechanics:molecular mechanics (QM:MM) calculations supported that triethanolamine stabilized the drug-CD interactions for the conformer identified in the 2D-ROESY experiments, improving the quality and uniformity of the formed complex. The role played by the co-solvent in the ternary complexes depends on its specific ability to interact with the CD cavity in the presence of the drug, which can be predicted in theoretical studies to select the best candidate.
authors.affiliation: Department of Pharmacy, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil. Electronic address: arthurmedeiros@ymail.com.
authors.forename: Arthur S A
authors.initials: ASA
authors.lastname: de Medeiros
authors.affiliation: Research and Pharmaceutical Technology Development Unit (UNITEFA, CONICET-UNC) and Department of Pharmacy, Faculty of Chemical Sciences, National University of Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina. Electronic address: ariana@fcq.unc.edu.ar.
authors.forename: Ariana
authors.initials: A
authors.lastname: Zoppi
authors.affiliation: Department of Pharmacy, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil. Electronic address: euzebiogb@gmail.com.
authors.forename: Euzébio G
authors.initials: EG
authors.lastname: Barbosa
authors.affiliation: Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil. Electronic address: jonasivan@gmail.com.
authors.forename: Jonas I N
authors.initials: JIN
authors.lastname: Oliveira
authors.affiliation: Department of Pharmacy, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil. Electronic address: mpedrosa@ufrnet.br.
authors.forename: Matheus F
authors.initials: MF
authors.lastname: Fernandes-Pedrosa
authors.affiliation: Research and Pharmaceutical Technology Development Unit (UNITEFA, CONICET-UNC) and Department of Pharmacy, Faculty of Chemical Sciences, National University of Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina. Electronic address: mrlcor@fcq.unc.edu.ar.
authors.forename: Marcela R
authors.initials: MR
authors.lastname: Longhi
authors.affiliation: Department of Pharmacy, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil. Electronic address: arnobiosilva@gmail.com.
authors.forename: Arnóbio A
authors.initials: AA
authors.lastname: da Silva-Júnior
mesh_terms: D002236:Carbohydrate Conformation; D004337:Drug Carriers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics; D014221:Triamcinolone / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D012997:Solvents; D047392:beta-Cyclodextrins; D014221:Triamcinolone; C031215:betadex
keywords: 1-Methyl-2-pyrrolidinone (PubChem CID: 13387); Beta-cyclodextrin (PubChem CID: 444041); Co-solvents; Cyclodextrins; Hydroxipropil-beta-cyclodextrin (PubChem CID: 14049689); Methyl-beta-cyclodextrin (PubChem CID: 162771); Oligosaccharides; Supramolecular aggregates; Ternary complexes; Triamcinolone; Triamcinolone (PubChem CID: 31307); Triethanolamine (PubChem CID: 7618)