Analysis of absorption enhancers in epithelial cell models.
A variety of chemical compounds are currently being discussed as novel drug delivery strategies. One promising strategy is to selectively open the paracellular pathway of epithelia for the passage of macromolecules. A prerequisite for this effect is a rapid and reversible action of these compounds, to allow a marked translocation of a drug, but also to avoid unwanted adverse effects, such as the translocation of noxious agents. Bioactive molecules that elevate paracellular permeability include Ca(2+) chelators, bacterial toxins, and other compounds, some of which perturb the structural basis of epithelial barrier function--the tight junction. Within the tight junction, organ- and tissue-specific barrier properties are determined mainly by claudins. The majority of members of the claudin protein family seal the paracellular pathway. This paper focuses on recent approaches concerning absorption-enhancing effects, with regard to selectivity and mechanism.
Institute of Clinical Physiology, Campus Benjamin Franklin, Charité- Universitätsmedizin Berlin, Freie Universität and Humboldt Universität, Berlin, Germany.
Rita
R
Rosenthal
Miriam S
MS
Heydt
Maren
M
Amasheh
Christoph
C
Stein
Michael
M
Fromm
Salah
S
Amasheh
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000378:metabolism; D048271:Chitosan / Q000378:metabolism; D004768:Enterotoxins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008962:Models, Theoretical; D019108:Tight Junctions
D002614:Chelating Agents; D004768:Enterotoxins; D005227:Fatty Acids; C035598:enterotoxin, Clostridium; D048271:Chitosan; D002118:Calcium