Global assembling of Academicians, Researchers, Scholars & Industry to disseminate and exchange information at 100+ Allied Academics Conferences
Dr. Craig Russell always had a strong interest in science and in particular human biology, health and disease and the associated interventions. His undergraduate degree in Human Biology mapped onto this interest and included molecular and cellular biology, biochemistry and physiology modules among others, which would carry relevance in the physiology and pharmacology setting he progressed into. He further developed his knowledge and bolstered his interest in these fields during his PhD. During this period, formulation of oral liquid antihypertensives formed the initial stages of my project; here an understanding of the chemical and physical properties of drug molecules as well as drug action on a molecular level in a physiological setting was essential. In vitro and In vivo characterisation of developed formulations utilising cell and rodent based models paved the way for subsequent genomic investigations into intestinal transporter expression profiling using microarray technology and bioinformatics. Cell culture played a key role during a spin off project which he have been developing in parallel with the main path of research which has seen the isolation and characterisation of a novel primary cell line aimed at delineation of gustatory sensation.
Microarrays 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.