In vitro toxicity and permeation of cyclodextrins in Calu-3 cells.
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.
Matilainen
Laura
L
Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. laura.matilainen@uku.fi
Toropainen
Tarja
T
Vihola
Henna
H
Hirvonen
Jouni
J
Järvinen
Tomi
T
Jarho
Pekka
P
Järvinen
Kristiina
K
D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D003505:Cyclodextrins / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000493:pharmacokinetics / Q000633:toxicity; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans
D003505:Cyclodextrins; D004337:Drug Carriers