title: Carboxymethyl and hydrazide functionalized β-cyclodextrin derivatives: a systematic investigation of complexation behaviours with the model hydrophobic drug dexamethasone.
abstract: Cyclodextrins (CDs) are typically functionalized to increase their solubility or provide reactive functional groups suitable for grafting onto polymer supports designed for controlled release applications. In this work, a systematic investigation was performed on the binding behaviour of the model drug dexamethasone with βCD derivatives functionalized with a small, negatively charged moiety (carboxyl groups, CM) and a large, neutral, reactive moiety (hydrazide groups, Hzd), both free and grafted to dextran. Solubilization capacities and thermodynamic parameters were examined through phase solubility analysis, the method of continuous variation, and isothermal titration calorimetry. Alternate mechanisms of solubilization were also investigated by probing aggregation of both free and complexed βCD derivatives using nanoparticle tracking analysis. CM/βCD and Hzd/βCD derivatives exhibited similar complexation behaviours with dexamethasone: 1:1 stoichiometry, linear phase solubility profiles, and consistent binding enthalpies. Increased functionalization reduced the complex stability constant as well as the complexation efficiency, while polymer grafting resulted in no significant change in binding properties. CM/βCD derivatives complexed with dexamethasone formed more and larger aggregates, while Hzd/βCD derivatives formed significantly fewer, smaller aggregates and dextran-grafted βCD did not aggregate. Such characterization of βCD derivatives provides a framework for designing βCDs as pharmaceutical excipients or drug binding sites in drug delivery vehicles.
authors: School of Biomedical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L7, Canada.
authors: Rabia
authors: R
authors: Mateen
authors: School of Biomedical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L7, Canada; Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L7, Canada. Electronic address: hoaretr@mcmaster.ca.
authors: Todd
authors: T
authors: Hoare
mesh_terms: D000272:Adipates / Q000737:chemistry; D003907:Dexamethasone / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D010316:Particle Size; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000272:Adipates; D047392:beta-Cyclodextrins; C441457:carboxymethyl-beta-cyclodextrin; D003907:Dexamethasone; C010011:adipic dihydrazide
keywords: Binding parameters; Dexamethasone; Functionalized cyclodextrins; Host–guest interactions; Inclusion complexes; Solubilization