RRC ID 44116
Author Verstraelen J, Reichl S.
Title Expression analysis of MDR1, BCRP and MRP3 transporter proteins in different in vitro and ex vivo cornea models for drug absorption studies.
Journal Int J Pharm
Abstract Ocular drug absorption studies are required for the development of new drugs or drug delivery systems for eye treatment. Such preclinical investigations on transcorneal drug absorption are performed ex vivo with the excised corneas of experimental animals or in vitro using corneal cell culture models. The data currently available on the expression of ABC transporter proteins in corneal tissue is limited or contradictory. This study describes, for the first time, the comparison of the expression of ABC transporters, in particular, MDR1, BCRP and MRP3, between human cornea cell culture models and the most commonly used ex vivo models, namely, rabbit and porcine corneas, conducted in the same laboratory. The expression levels and functionality were determined by means of PCR, western blot, immunohistochemistry and bidirectional permeation studies using specific substrates and inhibitors. The results clearly indicate species-dependent expression of the studied efflux transporters. In the rabbit cornea, the expression and activity of MDR1 transporter was confirmed, whereas human cell culture models and porcine corneas did not show MDR1 expression. However, human cornea models possessed MRP3 and BCRP expression, whereas no functional expression was found in rabbit and porcine corneas. Therefore, the translation of transcorneal permeation data from animal experiments to humans should be performed with caution.
Volume 441(1-2)
Pages 765-75
Published 2013-1-30
DOI 10.1016/j.ijpharm.2012.10.007
PII S0378-5173(12)00947-7
PMID 23069916
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics* ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters / genetics* Administration, Ophthalmic Animals Blotting, Western Caco-2 Cells Cells, Cultured Cornea / metabolism* Drug Delivery Systems Gene Expression Humans Models, Animal Multidrug Resistance-Associated Proteins / genetics* Neoplasm Proteins / genetics* Polymerase Chain Reaction Rabbits Species Specificity Swine
IF 3.862
Times Cited 12
Human and Animal Cells