Intestinal Safety of Water-soluble β-Cyclodextrins in Paediatric Oral Solutions of Spironolactone: Effects on Human Intestinal Epithelial Caco-2 Cells

Effects of water-soluble β-cyclodextrins (βCDs) on intestinal epithelial integrity were investigated, to establish the safe use of these βSCDs as solubilizers of spironolactone in paediatric enteral solutions. Mannitol permeability and transepithelial resistance (TER) of human intestinal epithelial Caco-2 cell monolayers during exposure to dimethyl-β-cyclodextrin (DMβCD), hydroxypropyl-β-cyclodextrin (HPβCD) and sulphobutyl ether β-cyclodextrin (SBEβCD) were followed. Staining methods were used to discern cells with damaged membranes and to study the integrity of cytoskeletal actin and tight junctions. Cytotoxicity of the βCDs was tested by effects on intracellular dehydrogenase activity. Exposure to HPβSCD and SBEβCD solutions had only minor effects on the integrity of Caco-2 cell monolayers. In contrast, DMβCD clearly increased the epithelial permeability for the hydrophilic marker [14C]mannitol across Caco-2 monolayers, decreased TER and showed a dose-dependent cytotoxicity. According to staining, DMβCD increased the permeability of the apical cell membrane without discernable effects on cytoskeletal actin. HPβCD and SBEβCD appear to be safe additives for use in enteral spironolactone preparations with respect to their acute local effects on epithelial integrity.