Faculty Collaboration Database

Microarray Determination of the Expression of Drug Transporters in Humans and Animal Species Used for the Investigation of Nasal Absorption. Mol Pharm 2015 Aug 03;12(8):2742-54

Date

06/25/2015

Pubmed ID

26106909

Pubmed Central ID

PMC4671632

DOI

10.1021/acs.molpharmaceut.5b00103

Scopus ID

2-s2.0-84938320961 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

Mice and rats are commonly used to investigate in vivo nasal drug absorption, yet their small nasal cavities limit their use for in vitro investigations. Bovine tissue explants have been used to investigate drug transport through the nasal respiratory and olfactory mucosae, yet limited information is available regarding the similarities and differences among these animal models compared to humans. The aim of this study was to compare the presence of a number of important drug transporters in the nasal mucosa of these species. DNA microarray results for nasal samples from humans, rats, and mice were obtained from GenBank, while DNA microarray and RT-PCR were performed on bovine nasal explants. The drug transporters of interest include multidrug resistance, cation, anion, peptide, and nucleoside transporters. Each of the species (mouse, rat, cattle, and human) shows similar patterns of expression for most of the important drug transporters. Several transporters were highly expressed in all the species, including MRP1, OCTN2, PEPT2, and y+LAT2. While some differences in transporter mRNA and protein expression were observed, the transporter expression patterns were quite similar among the species. The differences suggest that it is important to be aware of any specific differences in transporter expression for a given compound being investigated, yet the similarities support the continued use of these animal models during preclinical investigation of intranasally administered therapeutics.

Author List

Al-Ghabeish M, Scheetz T, Assem M, Donovan MD

Author

Mahfoud Assem PharmD Associate Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Intranasal
Animals
Biological Transport
Cattle
Gene Expression Profiling
Humans
Mice
Multidrug Resistance-Associated Proteins
Nasal Absorption
Nasal Mucosa
Nucleoside Transport Proteins
Oligonucleotide Array Sequence Analysis
Organic Cation Transport Proteins
Rats
Species Specificity