Gemcitabine anticancer activity enhancement by water soluble celecoxib/sulfobutyl ether-β-cyclodextrin inclusion complex.

Autor: Rescifina A; Department of Drug Sciences, University of Catania, V.le A. Doria, 6 - 95125 Catania, Italy. Electronic address: arescifina@unict.it., Surdo E; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno D'Alcontrés, 31 - 98166 Messina, Italy. Electronic address: emi983@hotmail.it., Cardile V; Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia, 97 - 95125 Catania, Italy. Electronic address: cardile@unict.it., Avola R; Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia, 97 - 95125 Catania, Italy. Electronic address: a.rosanna85@libero.it., Eleonora Graziano AC; Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia, 97 - 95125 Catania, Italy. Electronic address: acegraz@unict.it., Stancanelli R; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno D'Alcontrés, 31 - 98166 Messina, Italy. Electronic address: rstancanelli@unime.it., Tommasini S; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno D'Alcontrés, 31 - 98166 Messina, Italy. Electronic address: stommasini@unime.it., Pistarà V; Department of Drug Sciences, University of Catania, V.le A. Doria, 6 - 95125 Catania, Italy. Electronic address: vpistara@unict.it., Ventura CA; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno D'Alcontrés, 31 - 98166 Messina, Italy. Electronic address: caventura@unime.it.
Jazyk: angličtina
Zdroj: Carbohydrate polymers [Carbohydr Polym] 2019 Feb 15; Vol. 206, pp. 792-800. Date of Electronic Publication: 2018 Nov 20.
DOI: 10.1016/j.carbpol.2018.11.060
Abstrakt: We investigated the complexation of celecoxib (CCB) into sulfobuthyl-ether-β-cyclodextrin (SBE-β-CD) for the realization of an inhalable dry-powder formulation containing gemcitabine (GEM) for lung anticancer therapy. Complexation increased the water solubility of CCB (0.003 mg/mL and 0.834 mg/mL for CCB free and complexed, respectively) and produced a quantitative dissolution of the drug within 15 min. The CCB/SBE-β-CD inclusion complex showed a high stability constant (8131 M -1 ) not influenced by the presence of GEM in solution. Two-dimensional NMR experiments and computational studies demonstrated that the pyrazole ring of CCB penetrates deeper into SBE-β-CD from the secondary rim. The aromatic rings are positioned at the edge of the cavity, establishing hydrogen bonds with the SBE-β-CD that stabilized the complex. CCB showed limited cytotoxic activity on A549 cell lines. Complexation significantly increased activity passing from 30% to 45% cell mortality. Moreover, CCB/SBE-β-CD strongly improved the cytotoxicity of GEM, observing about 60% of cell mortality for the combined formulation.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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