Synthesis, Cytotoxicity, and Phase‐Solubility Study of Cyclodextrin Click Clusters. Issue 10 (20th August 2014)

• Record Type: Journal Article
• Authors: Le, Hoa Thi; Jeon, Hyun Mi; Lim, Choon Woo; Kim, Tae Woo
• Is Part Of: Journal of pharmaceutical sciences. Volume 103:Issue 10(2014:Oct.)
• Page Start: 3183
• Page End: 3189
• Publication Date: 2014-08-20
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.24107
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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‐<italic>O</italic>‐methyl}‐β‐cyclodextrin (HT‐β‐CD(OMe)<sub>2</sub>), and heptakis{6‐(4‐sulfonylmethyl‐1<italic>H</italic>‐[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)<sub>2</sub> 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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3183–3189, 2014</p> </abstract>