title: Optimization of acoustic liposomes for improved in vitro and in vivo stability.
abstract: OBJECTIVE
  Liposomes encapsulating perfluoropropane gas, termed acoustic liposomes (ALs), which can serve both for ultrasound (US) imaging and US-mediated gene delivery, have been reported. However, the echogenicity of ALs decreases within minutes in vivo due to gas diffusion and leakage, hindering time-consuming procedures such as contrast-enhanced 3D US imaging and raising the need for improvement of their stability.
  
  
  METHODS
  The stability of ALs preparations incorporating increasing ratios of anionic / unsaturated phospholipids, polyethylene glycol (PEG)ylated phospholipid and cholesterol was investigated by measurement of their reflectivity over time using a high-frequency US imaging system, both in vitro and in vivo.
  
  
  RESULTS
  The retention of echogenicity of ALs in vitro is enhanced with increasing molar ratios of PEGylated lipids. Addition of 10 molar percent of an anionic phospholipid resulted in a 31% longer half-life, while cholesterol had the opposite effect. Assessment of the stability of an optimized composition showed a more than 2-fold increase of the detection half-life in mice.
  
  
  CONCLUSIONS
  Presence of a PEG coating not only serves to provide "stealth" properties in vivo, but also contributes to the retention of the encapsulated gas. The optimized ALs reported here can be used as a contrast agent for lengthier imaging procedures.
authors.affiliation: Molecular Delivery System Laboratory Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-0872, Japan.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sax
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kodama
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000737:chemistry; D003287:Contrast Media / Q000008:administration & dosage*; D005466:Fluorocarbons / Q000008:administration & dosage*; D006207:Half-Life; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D010743:Phospholipids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D008081:Liposomes; D010743:Phospholipids; D011092:Polyethylene Glycols; D002784:Cholesterol; C042852:perflutren