title: Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated in vitro in cell cultures.
abstract: OBJECTIVE
  CriticalSorb™, with the principal component Solutol® HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol® HS15.
  
  
  METHODS
  Micelle size and CMC of Solutol® HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeability of a panel of biological drugs, and to assess changes in TEER, tight junction and F-actin morphology. The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2-10.
  
  
  RESULTS
  This work initially confirms surfactant-like behaviour of Solutol® HS15 in aqueous media, while subsequent experiments demonstrate that the effect of Solutol® HS15 on epithelial tight junctions is different from a 'classical' tight junction opening agent and illustrate the effect of Solutol® HS15 on the cell membrane (endocytosis rate) and F-actin cytoskeleton.
  
  
  CONCLUSIONS
  Solutol® HS15 is the principle component of CriticalSorb™ that has shown an enhancement in permeability of medium sized biological drugs across epithelia. This study suggests that its mechanism of action arises primarily from effects on the cell membrane and consequent impacts on the cell cytoskeleton in terms of actin organisation and tight junction opening.
authors.affiliation: Division of Drug Delivery and Tissue Engineering, School of Pharmacy Boots Science Building, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Saif
authors.initials: S
authors.lastname: Shubber
authors.forename: Driton
authors.initials: D
authors.lastname: Vllasaliu
authors.forename: Cyril
authors.initials: C
authors.lastname: Rauch
authors.forename: Faron
authors.initials: F
authors.lastname: Jordan
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Illum
authors.forename: Snjezana
authors.initials: S
authors.lastname: Stolnik
mesh_terms: D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D020014:K562 Cells; D008823:Micelles; D009092:Mucous Membrane / Q000378:metabolism*; D010539:Permeability; D011092:Polyethylene Glycols / Q000378:metabolism*; D012995:Solubility; D013229:Stearic Acids / Q000378:metabolism*
chemical_list: D008823:Micelles; D013229:Stearic Acids; D011092:Polyethylene Glycols; C067028:Solutol HS 15