title: Recent progress in tight junction modulation for improving bioavailability.
abstract: BACKGROUND
  Currently, there are many novel drugs that belong to class III or IV of the Biopharmaceutics Classification System, showing low bioavailability. Tight junction (TJ) modulation offers an approach to increase bioavailability of pharmaceutical compounds. Furthermore, some diseases are accompanied by disturbed barrier function or TJ dysregulation and thus represent a second application for TJ modulators.
  
  
  METHODS
  This review contains a summary of three different TJ modulators: AT1002, PN159 and labradimil. Within this summary, the authors provide a description of their effects on TJs, their adverse effects and their success in clinical trials. Furthermore, the authors present the current understanding of TJ regulation and highlight opportunities to develop new TJ modulators; they also review the problems that might occur.
  
  
  CONCLUSIONS
  The development of new mechanism-based (MB) TJ modulators is a very promising field of research. MB approaches are expected to have the best future prospects. Further elucidation of signaling pathways and TJ regulation will be necessary for advancing MB TJ modulator research.
authors.affiliation: Technische Universität Braunschweig, Institut für Pharmazeutische Technologie , Mendelssohnstr. 1, Braunschweig 38106 , Germany s.reichl@tu-bs.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Saaber
authors.forename: Sabrina
authors.initials: S
authors.lastname: Wollenhaupt
authors.forename: Knut
authors.initials: K
authors.lastname: Baumann
authors.forename: Stephan
authors.initials: S
authors.lastname: Reichl
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology / Q000627:therapeutic use; D001682:Biological Availability; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D019108:Tight Junctions / Q000378:metabolism*
chemical_list: C530561:AT1002; D023181:Antimicrobial Cationic Peptides; C547315:KLAL peptide; D009842:Oligopeptides; C089876:RMP 7; D001920:Bradykinin