title: Drug delivery studies in Caco-2 monolayers. IV. Absorption enhancer effects of cyclodextrins.
abstract: OBJECTIVE
  The purpose of the present study was to use the human colorectal carcinoma cell line. Caco-2, as a human intestinal epithelial model for studying the effects of cyclodextrins as absorption enhancers.
  
  
  METHODS
  Cyclodextrins of varying sizes and physicochemical characters were investigated. The effects of the cyclodextrins were evaluated by means of staining of the cytoplasma and determination of the mitochondrial dehydrogenase activity as well as by transport enhancement of the macromolecular pore marker polyethylene glycol 4000 (PEG-4000) across the Caco-2 monolayers.
  
  
  RESULTS
  The transport enhancing properties of the cyclodextrins were found to follow the lipophilicity of the core in their cyclic structure. Dimethyl-beta-cyclodextrin was the most powerful in all aspects and caused an increase in the permeability of the cytoplasma membrane in a concentration dependent manner. It was possible to increase the overall transport of PEG-4000 10-fold by the use of dimethyl-beta-cyclodextrin in low concentrations where the toxic effects on the monolayers were insignificant. It was further observed that the basolateral membrane was significantly more sensitive to cyclodextrins than the apical membrane.
  
  
  CONCLUSIONS
  Since dimethyl-beta-cyclodextrin was able to produce an absorption enhancing effect on PEG-4000 in concentrations where the toxic effects on Caco-2 monolayers were low it is worth to pursue the compound as an absorption enhancer.
authors.affiliation: Royal Danish School of Pharmacy, Department of Pharmaceutics, Copenhagen O, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Hovgaard
authors.forename: H
authors.initials: H
authors.lastname: Brøndsted
mesh_terms: D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D003505:Cyclodextrins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism; D004337:Drug Carriers; D016503:Drug Delivery Systems; D017097:Electric Impedance; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D046911:Macromolecular Substances; D008928:Mitochondria / Q000201:enzymology; D008954:Models, Biological; D009994:Osmolar Concentration; D010088:Oxidoreductases / Q000378:metabolism; D011092:Polyethylene Glycols / Q000493:pharmacokinetics
chemical_list: D003505:Cyclodextrins; D004337:Drug Carriers; D046911:Macromolecular Substances; D011092:Polyethylene Glycols; D010088:Oxidoreductases