[en] Cyclodextrins (CDs) are promising solubility enhancers for inhaled drug delivery. However, they have dose-dependent effects on the respiratory epithelium, which may have advantages for permeability enhancement but also gives rise to safety concerns. In this study, the methyl thiazol tetrazolium (MTT) assay was used to compare a new sparingly methylated β-CD, Kleptose® Crysmeβ (Crysmeb) with the more established CD derivatives hydroxypropyl-γ-cyclodextrin (HPγCD), randomly methylated β-cyclodextrin (Rameb) and hydroxypropyl-β-cyclodextrin (HPβCD). The βCD derivatives affected cell metabolism in A549 cells in a concentration dependent manner with LDso of 56, 31 and 11 mM obtained for HPβCD, Crysmeb and Rameb, respectively. Calu-3 cells were less susceptible to βCD with an LDso of 25 mM being obtained for Rameb only. Permeability increases in Calu-3 cell layers were observed with βCD derivatives and a concentration dependency shown. The mechanism of permeability enhancement and its reversibility was investigated. Rameb produced an irreversible loss of cell layer barrier function at ≥25 mM, but perturbations of epithelial integrity were moderate and reversible in the case of HPβCD and Crysmeb (25-50 mM). Given its high solubilisation capacity, the low toxicity and transient absorption promoting properties, this study identifies Crysmeb as a promising adjuvant in formulations for inhalation.