Development of a human mammary epithelial cell culture model for evaluation of drug transfer into milk.
In the present study, a human mammary epithelial cell (HMEC) culture model was developed to evaluate the potential involvement of carrier-mediated transport systems in drug transfer into milk. Trypsin-resistant HMECs were seeded on Matrigel-coated filters to develop monolayers of functionally differentiated HMEC. Expression of the specific function of HMEC monolayers was dependent of the number of trypsin treatments. Among the monolayers with different numbers of treatment (treated 1 to 3 times), the monolayer treated 3 times (3-t-HMEC monolayer) showed the highest maximal transepithelial resistance and expression of beta-casein mRNA as an index of differentiation. Transport of tetraethylammonium (TEA) across the 3-t-HMEC monolayer in the basolateral-to-apical direction was significantly higher than that in the apical-to-basolateral direction (p < 0.05), whereas such directionality was not observed for p-amino-hippurate, suggesting the existence of organic cation transporters, but not organic anion transporters. In fact, expression of mRNAs of human organic cation transporter (OCT) 1 and 3 were detected in the 3-t-HMEC monolayer. These results indicate that the 3-t-HMEC monolayer is potentially useful for the evaluation of carrier-mediated secretion of drugs including organic cations into human milk.
Kimura
Soichiro
S
Hospital Pharmacy, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
Morimoto
Keiko
K
Okamoto
Hiroshi
H
Ueda
Hideo
H
Kobayashi
Daisuke
D
Kobayashi
Jun
J
Morimoto
Yasunori
Y
D001692:Biological Transport; D002364:Caseins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line / Q000166:cytology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007774:Lactation / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008895:Milk, Human / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019789:Tetraethylammonium / Q000378:metabolism; D014357:Trypsin / Q000494:pharmacology; D000099254:Organic Cation Transporter 3
D002364:Caseins; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D012333:RNA, Messenger; D019789:Tetraethylammonium; D014357:Trypsin; D000099254:Organic Cation Transporter 3