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August 17-18, 2017 | Toronto, Canada
ANNUAL BIOTECHNOLOGY CONGRESS
Ann Biol Sci, 2017
ISSN: 2348-1927
Application of microarrays to develop an
in vitro
–
in vivo
correlation screening toolbox
Craig Russell
1
, Sumyra Begum
2
, Yasar Hussain
2
, Majad Hussain
2
, David Huen
3
, Ayesha S Rahman
3
, Yvonne Perrie
4
and
Afzal R Mohammed
1
1
Aston University, UK
2
Pharmaspec Ltd., UK
3
University of Wolverhampton, UK
4
University of Strathclyde, UK
M
icroarrays are powerful tools utilised in genomics
allowing high throughput analysis of mRNA
abundance. They have found application in many areas of
drug discovery and development including comparative
assessment of normal and diseased state tissues,
transcription and expression profiling, side-effect profiling,
pharmacogenomics and identification of biomarkers. In this
application they were utilised to examine Caco-2 cells used
in transport studies, investigating potential correlations
between expression flux of genes coding for transpoter
proteins known to interact with model drugs, and
in vitro
and
in vivo
permeability of the drugs, with a view towards
developing a tool for predicting drug bioavailability early
in the drug development pipeline. Lisinopril, Ramipril and
Spironolactone formulations developed in house were
used as model formulations.
In vitro
and
in vivo
uptake data
was gathered for each formulation and focus was on genes
coding transporters ABCB1, SLC15A1, SLC15A2, ABCC2 and
SLCO1A2 following microarray analysis. Shortlisted genes
of interest, all exhibited non-significant flux in expression
levels in Caco-2 following analysis after transport studies
using model formulations. There were however numerous
SLC and ABC genes for which the expression had changed
significantly. These were subsequently investigated using
the Koyoto Encyclopaedia of Genes and Genomes (KEGG) to
identify their function and seek clarity about the findings.
Athough no clear cut revelations were derived from this
study, the data strongly suggested that further research is
warranted in this area, where future work intends to utilise
a much larger formulation repertoire in conjunction with
novel computational approaches currently in development
to illucidate trends.
Speaker Biography
Craig Russell has completed his BSc (Hons) in Human Biology at the University of
Huddersfield in 2010 and later obtained his PhD from Aston University. After which,
he carried out his Post-doctoral research in the same institution. Upon completion of
this work, he then became a Lecturer in Physiology and Pharmacology at Coventry
University College before recently returing to Aston University in his current position
as Lecturer in Pharmacy. He has multiple publications in reputable journals and serves
as an Editorial Board Member for the
Journal of Research and Reviews: Drug delivery
.
e:
c.russell6@aston.ac.ukCraig Russell et al., Ann Biol Sci, 2017, 5:3
DOI: 10.21767/2348-1927-C1-002