TY - JOUR
T1 - Mucus can change the permeation rank order of drug candidates
AU - Hagesaether, Ellen
AU - Christiansen, Elisabeth
AU - Due-Hansen, Maria Elisabeth
AU - Ulven, Trond
N1 - Copyright © 2013 Elsevier B.V. All rights reserved.
PY - 2013
Y1 - 2013
N2 - The aim of the study was to test the effect of mucus on the permeability of newly developed structurally related free fatty acid receptor 1-agonists TUG-488, TUG-499 and TUG-424, which were compared to the more hydrophilic ketoprofen and the more hydrophobic testosterone as reference drugs. The model membrane was cell monolayers consisting of methotrexate treated HT29 cells grown for approximately one, two or three weeks, and thereby differing in the amount of goblet cells and hence mucus. The results show that the permeation of all compounds was high and that mucus in most cases only had a minor influence. However, for one of the drug candidates, TUG-499, mucus had a clear impact, and this could not be explicitly related to the hydrophobicity of this compound. Secreted mucus thus changed the obtained rank order of permeation. This was especially apparent when the experiments were carried out at a lower agitation. These results indicate that an experimental system without mucus can give a faulty rank order of permeation compared to mucous membranes when structurally related drug candidates are tested.
AB - The aim of the study was to test the effect of mucus on the permeability of newly developed structurally related free fatty acid receptor 1-agonists TUG-488, TUG-499 and TUG-424, which were compared to the more hydrophilic ketoprofen and the more hydrophobic testosterone as reference drugs. The model membrane was cell monolayers consisting of methotrexate treated HT29 cells grown for approximately one, two or three weeks, and thereby differing in the amount of goblet cells and hence mucus. The results show that the permeation of all compounds was high and that mucus in most cases only had a minor influence. However, for one of the drug candidates, TUG-499, mucus had a clear impact, and this could not be explicitly related to the hydrophobicity of this compound. Secreted mucus thus changed the obtained rank order of permeation. This was especially apparent when the experiments were carried out at a lower agitation. These results indicate that an experimental system without mucus can give a faulty rank order of permeation compared to mucous membranes when structurally related drug candidates are tested.
U2 - 10.1016/j.ijpharm.2013.05.036
DO - 10.1016/j.ijpharm.2013.05.036
M3 - Journal article
SN - 0378-5173
VL - 452
SP - 276
EP - 282
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -