Genomic evaluation during permeability of indomethacin and its solid dispersion

Sheraz Khan, Amr Elshaer, Ayesha S Rahman, Peter Hanson, Yvonne Perrie, Afzal-Ur-Rahman Mohammed

Research output: Contribution to journalArticle

Abstract

Drug resistance was first identified in cancer cells that express proteins known as multidrug resistance proteins that extrude the therapeutic agents out of the cells resulting in alteration of pharmacokinetics, tissue distribution, and pharmacodynamics of drugs. To this end studies were carried out to investigate the role of pharmacological inhibitors and pharmaceutical excipients with a primary focus on P-glycoprotein (P-gp). The aim of this study was to investigate holistic changes in transporter gene expression during permeability upon formulation of indomethacin as solid dispersion. Initial characterization studies of solid dispersion of indomethacin showed that the drug was dispersed within the carrier in amorphous form. Analysis of permeability data across Caco-2 monolayers revealed that drug absorption increased by 4-fold when reformulated as solid dispersion. The last phase of the work involved investigation of gene expression changes of transporter genes during permeability. The results showed that there were significant differences in the expression of both ATP-binding cassette (ABC) transporter genes as well as solute carrier transporter (SLC) genes suggesting that the inclusion of polyethylene glycol as well as changes in molecular form of drug from crystalline to amorphous have a significant bearing on the expression of transporter network genes resulting in differences in drug permeability. © 2011 Informa UK, Ltd.

LanguageEnglish
Pages615-623
Number of pages9
JournalJournal of Drug Targeting
Volume19
Issue number8
DOIs
Publication statusPublished - Sep 2011

Fingerprint

Indomethacin
Permeability
Pharmaceutical Preparations
Genes
P-Glycoproteins
Gene Expression
ATP-Binding Cassette Transporters
Gene Regulatory Networks
Excipients
P-Glycoprotein
Tissue Distribution
Drug Resistance
Pharmacokinetics
Pharmacology
Neoplasms
Proteins

Keywords

  • caco-2 cells
  • indomethacin
  • microarray
  • permeability
  • solid dispersion

Cite this

Khan, Sheraz ; Elshaer, Amr ; Rahman, Ayesha S ; Hanson, Peter ; Perrie, Yvonne ; Mohammed, Afzal-Ur-Rahman. / Genomic evaluation during permeability of indomethacin and its solid dispersion. In: Journal of Drug Targeting. 2011 ; Vol. 19, No. 8. pp. 615-623.
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Genomic evaluation during permeability of indomethacin and its solid dispersion. / Khan, Sheraz; Elshaer, Amr; Rahman, Ayesha S; Hanson, Peter; Perrie, Yvonne; Mohammed, Afzal-Ur-Rahman.

In: Journal of Drug Targeting, Vol. 19, No. 8, 09.2011, p. 615-623.

Research output: Contribution to journalArticle

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