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

被引：41
作者：
Rescifina, Antonio [1 ]
Surdo, Emanuela [2 ]
Cardile, Venera [3 ]
Avola, Rosanna [3 ]
Graziano, Adriana Carol Eleonora [3 ]
Stancanelli, Rosanna [2 ]
Tommasini, Silvana [2 ]
Pistara, Venerando [1 ]
Ventura, Cinzia Anna [2 ]
机构：
[1] Univ Catania, Dept Drug Sci, Vle A Doria 6, I-95125 Catania, Italy
[2] Univ Messina, Dept Chem Biol Pharmaceut & Environm Sci, Vle F Stagno Dalcontres 31, I-98166 Messina, Italy
[3] Univ Catania, Dept Biomed & Biotechnol Sci, Via Santa Sofia 97, I-95125 Catania, Italy
来源：
CARBOHYDRATE POLYMERS | 2019年 / 206卷
关键词：
Celecoxib; Sulfobutyl-ether-beta-cyclodextrin; Gemcitabine; NMR spectroscopy; Computational studies; In vitro biological studies; CELL LUNG-CANCER; IN-VITRO; PHASE-II; PHYSICOCHEMICAL CHARACTERIZATION; ANTIINFLAMMATORY ACTIVITY; EQUILIBRIUM-CONSTANTS; DOWN-REGULATION; FORCE-FIELDS; CELECOXIB; DOCETAXEL;
D O I：
10.1016/j.carbpol.2018.11.060
中图分类号：
O69 [应用化学];
学科分类号：
081704 ;
摘要：
We investigated the complexation of celecoxib (CCB) into sulfobuthyl-ether-beta-cyclodextrin (SBE-beta 1-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-beta-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-beta-CD from the secondary rim. The aromatic rings are positioned at the edge of the cavity, establishing hydrogen bonds with the SBE-beta-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-beta-CD strongly improved the cytotoxicity of GEM, observing about 60% of cell mortality for the combined formulation.
引用
收藏
页码：792 / 800
页数：9
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