title: Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation.
abstract: BACKGROUND
  Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery.
  
  
  METHODS
  Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS)-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH.
  
  
  RESULTS
  The optimal formulation showed an insulin entrapment efficiency of 30% ± 2% and a particle size of 154 ± 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and α-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate.
  
  
  CONCLUSIONS
  Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Niu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Lars
authors.initials: L
authors.lastname: Hovgaard
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002942:Circular Dichroism; D004355:Drug Stability; D010450:Endopeptidases / Q000378:metabolism*; D006000:Glycocholic Acid / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061386:Insulin, Regular, Human / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011312:Pressure
chemical_list: D061386:Insulin, Regular, Human; D008081:Liposomes; D010450:Endopeptidases; D006000:Glycocholic Acid