title: Colloidal structures in media simulating intestinal fed state conditions with and without lipolysis products.
abstract: OBJECTIVE
  To study the ultrastructure of biorelevant media and digestion products of self-nanoemulsifying drug delivery system (SNEDDS) at high level BS/PL conditions.
  
  
  METHODS
  Cryogenic transmission electron microscopy (Cryo-TEM) was employed to visualize the colloid structures in the biorelevant media and lipolytic products generated during hydrolysis of a SNEDDS formulation. Their electrical properties were investigated by measuring their zeta-potential values.
  
  
  RESULTS
  In the biorelevant media, vesicles (either unilamellar or multilamellar) and bilayer fragments are visualized. Occasionally, vesicles with an internal deformed structure are recognized, suggesting surface tension or uneven lateral stress. Visualization studies of the intermediate colloidal phases produced during digestion of a SNEDDS using the in vitro lipolysis model revealed the formation of similar structures as previously reported. The zeta-potential of the media was negatively charged and decreased from -23 to -35 mV with increasing surfactant/lipid load. Lower zeta-potential values (-16 mV) obtained for the structures formed during the lipid hydrolysis of the SNEDDS were probably due to the presence of calcium, which shields the surface, thereby reducing the charge.
  
  
  CONCLUSIONS
  The diversity of these vesicles in terms of size, lamellarity, and internal organization advocate their important role during lipid digestion in the gastrointestinal milieu.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, The Faculty of Pharmaceutical Science, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark. df@dfuni.dk
authors.forename: Dimitrios G
authors.initials: DG
authors.lastname: Fatouros
authors.forename: Isabelle
authors.initials: I
authors.lastname: Walrand
authors.forename: Bjorn
authors.initials: B
authors.lastname: Bergenstahl
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003102:Colloids; D004337:Drug Carriers; D005989:Glycerides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007413:Intestinal Mucosa / Q000378:metabolism*; D007419:Intestinal Secretions / Q000737:chemistry* / Q000378:metabolism; D008066:Lipolysis; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures; D019301:Oleic Acid / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D019518:Postprandial Period; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013656:Taurocholic Acid / Q000737:chemistry; D013997:Time Factors
chemical_list: D003102:Colloids; D004337:Drug Carriers; D005989:Glycerides; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D019301:Oleic Acid; D013656:Taurocholic Acid; C005953:monoolein; D002118:Calcium