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  • Title: In vitro toxicity and permeation of cyclodextrins in Calu-3 cells.
    Author: Matilainen L, Toropainen T, Vihola H, Hirvonen J, Järvinen T, Jarho P, Järvinen K.
    Journal: J Control Release; 2008 Feb 18; 126(1):10-6. PubMed ID: 18160169.
    Abstract:
    Cyclodextrins (CDs) can improve the pulmonary drug delivery by increasing aqueous solubility, absorption and bioavailability of drugs. Although the systemic absorption of CDs from gastrointestinal tract is very limited, their systemic absorption after pulmonary administration cannot be excluded. The aims of this study were 1) to evaluate the in vitro toxicity of various CDs (alpha-, beta-, gamma-, hydroxypropyl-alpha-, hydroxypropyl-beta- and randomly methylated-beta-CD) in pulmonary Calu-3 cells and Calu-3 cell layers using MTT and LDH cytotoxicity tests, and 2) to study the permeation of natural CDs (alpha-, beta- and gamma-CD) at non-toxic concentrations across Calu-3 cell layers. Randomly methylated-beta-CD evoked cell death and membrane damage in Calu-3 cells at lower concentrations compared to the other CDs tested. In terms of their toxicity, gamma-CD, hydroxypropyl-beta-CD and hydroxypropyl-alpha-CD were the safest to the Calu-3 cells. Based on the cumulative penetrated amount at 4 h, the apparent permeability coefficients for alpha-, beta- and gamma-CD were 6.77+/-2.23 x 10(-8), 6.68+/-0.84 x 10(-8) and 6.71+/-0.74 x 10(-8) cm/s, respectively. In conclusion, this study indicates that 1) in terms of their local safety, hydroxypropylated CDs and natural gamma-CD seem to be the safest of the tested CDs in pulmonary drug delivery, and 2) cyclodextrins may be absorbed into the systemic circulation from the lungs.
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