title: Effects of cyclodextrins on drug delivery through biological membranes.
abstract: Cyclodextrins have proven themselves to be useful functional excipients. Cyclodextrin derivatives can be hydrophilic or relatively lipophilic based on their substitution and these properties can give insight into their ability to act as permeability enhancers. Lipophilic cyclodextrins such as the methylated derivatives are thought to increase drug flux by altering barrier properties of the membrane through component extraction or fluidization. The hydrophilic cyclodextrin family also modulate drug flux through membranes but via different mechanisms. The current effort seeks to provide various explanations for these observations based on interactions of hydrophilic cyclodextrins with the unstirred water layer that separates the bulk media from biological membranes such as the gastric mucosa, cornea and reproductive tract. Theories on the serial nature of resistances to drug flux are used to explain why hydrophilic cyclodextrins can enhance drug uptake in some situation (i.e., for lipophilic material) but not in others. In addition, the nature of secondary equilibria and competition between cyclodextrins and rheologically important biopolymers such as mucin are assessed to give a complete picture of the effect of these starch derivatives. This information can be useful not only in understanding the actions of cyclodextrin but also in expanding their application and uses.
authors.affiliation: Faculty of Pharmacy, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland. thorstlo@hi.is
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Loftsson
authors.forename: Stine Byskov
authors.initials: SB
authors.lastname: Vogensen
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Brewster
authors.forename: Fífa
authors.initials: F
authors.lastname: Konrádsdóttir
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers; D004339:Drug Compounding; D017097:Electric Impedance; D005079:Excipients / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D008954:Models, Biological; D015394:Molecular Structure; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D003505:Cyclodextrins; D004337:Drug Carriers; D005079:Excipients; D008055:Lipids; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D014867:Water