title: Synthesis, cytotoxicity, and phase-solubility study of cyclodextrin click clusters.
abstract: To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HT-β-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl}-β-cyclodextrin (HT-β-CD(OMe)2 ), and heptakis{6-(4-sulfonylmethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (ST-β-CD). The CCCs were prepared using copper(I)-catalyzed azide-alkyne cycloaddition from 6-azido-6-deoxy-β-CD and their water solubility, cytotoxicity, and drug-solubilizing effect were investigated. Water turbidity testing of the CCCs showed that the minimum water solubility of the CCCs is at least 20 times higher than that of β-CD. An MTT cell viability assay performed on HeLa cells demonstrated a low cytotoxicity of the CCCs compared with 2,6-dimethyl-β-cyclodextrin. HT-β-CD(OMe)2 and ST-β-CD did not demonstrate any cytotoxicity within the experimental concentration (∼5 mM) like 2-hydroxypropyl-β-CD. A phase-solubility study of prednisolone with the CCCs suggested that CCCs showed increased solubility of prednisolone in the presence of increasing concentrations of the CCCs. The comparison between the conventional CD derivatives and CCCs on solubility, cytotoxicity, and binding property implies that CCCs are alternative cyclodextrin derivatives useful for overcoming the restrictions of conventional cyclodextrin chemistry.
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do, 449-701, Republic of Korea.
authors.forename: Hoa Thi
authors.initials: HT
authors.lastname: Le
authors.forename: Hyun Mi
authors.initials: HM
authors.lastname: Jeon
authors.forename: Choon Woo
authors.initials: CW
authors.lastname: Lim
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Kim
mesh_terms: D003505:Cyclodextrins / Q000737:chemistry*; D011239:Prednisolone / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D003505:Cyclodextrins; D014867:Water; D011239:Prednisolone
keywords: complexation; copper(I)-catalyzed azide-alkyne cycloaddition; cyclodextrin click cluster; cyclodextrins; cytotoxicity; encapsulation; excipients; solubility