Mucin-based stationary phases as tool for the characterization of drug-mucus interaction

Andrea F.G. Gargano, Michael Lämmerhofer, Hans Lönn, Peter J. Schoenmakers, Tomas Leek

Research output: Chapter in Book / Report / Conference proceedingChapterAcademicpeer-review

Abstract

Mucin glycoproteins belong to a class of high molecular weight, heavy glycosylated, proteins that together with water, salts and lipids constitute mucous secretions. Particular disease states (e.g. obstructive chronic bronchitis and ovarian tumor) are known to modify the composition and the thickness of those barriers. Therefore, it is important to address whether the absorption of potential drug candidates to be administered is influenced by the presence of interaction with this class of proteins. Typically, the methods adopted to characterize drug-protein interaction are dialysis, ultrafiltration and gel filtration. Besides these, bio-affinity chromatographic methods have demonstrated to be valuable tools offering the advantageous characteristics such as simplicity, efficiency, high-throughput capability and robustness. The present contribution reports on the synthesis and analytical characterization of a new chromatographic stationary phase based on covalently immobilized mucin and explores the use of LC-UV affinity zonal chromatography as a tool to screen drugs for their affinity to mucin. A series of different binding chemistries for the covalent linkage of mucin to silica-based supports as well as distinct immobilization protocols (static and dynamic) have been evaluated in order to optimize surface coverage. Resultant stationary phases have been characterized chromatographically by studying the effect of mobile phase and analyte structure on the distribution and retention of test compounds. As conclusive study, we report the evaluation of the retention characteristics of 41 drug-like compounds (having heterogeneous chemical properties) for their interaction with this novel stationary phase. © 2014 Elsevier B.V.
Original languageEnglish
Title of host publicationJournal of Chromatography A
PublisherElsevier
Pages70-81
Number of pages12
Volume1351
ISBN (Print)0021-9673
DOIs
Publication statusPublished - 18 Jul 2014

Publication series

NameJournal of Chromatography A
Volume1351

Keywords

  • Affinity chromatography
  • Drug-protein affinity
  • Liquid chromatography
  • Mucin
  • Protein stationary phases

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