title: Gamma-irradiation of non-frozen, frozen, and freeze-dried liposomes.
abstract: OBJECTIVE
  The aim of this work was to investigate the possibilities and limitations of gamma-irradiation as a sterilisation method for nonfrozen, frozen, and freeze-dried liposomes.
  
  
  METHODS
  Liposomes with an average size of 0.2 micron were irradiated with doses up to about 5 x 10(4) Gy in a nitrogen atmosphere.
  
  
  RESULTS
  Phospholipids in dipalmitoylphosphatidycholine/dipalmitoylphosphatidylglycerol (DPPC/DPPG) 10/1-liposomes and egg phosphatidylcholine/egg phosphatidylglycerol (EPC/EPG) 10/1-liposomes in 10 mM phosphate buffer (pH 7.4) without trehalose degraded considerably upon gamma-irradiation. Irradiation damage was reduced in the presence of 10% trehalose added as a cryoprotectant, but trehalose reacted with species induced by gamma-irradiation as demonstrated by large decreases in pH. Both pH decrease and oxidative damage of EPC/EPG 10/1-liposomes were strongly dependent on the physical state during irradiation (nonfrozen, frozen or freeze-dried). No changes in liposomal size were found upon gamma-irradiation, and hardly any change was seen in bilayer rigidity. Differences in the gel-to-liquid phase transition of DPPC/DPPG 10/1-liposome dispersions before and after gamma-irradiation were small in the presence of 10% trehalose, but larger in the absence of trehalose.
  
  
  CONCLUSIONS
  The degradation of trehalose limits the use of freezing or freeze-drying liposome dispersions as a way to minimise irradiation damage.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), The Netherlands.
authors.forename: N J
authors.initials: NJ
authors.lastname: Zuidam
authors.forename: S S
authors.initials: SS
authors.lastname: Lee
authors.forename: D J
authors.initials: DJ
authors.lastname: Crommelin
mesh_terms: D016880:Anisotropy; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004161:Diphenylhexatriene; D005453:Fluorescence; D005612:Freeze Drying; D005615:Freezing; D005720:Gamma Rays; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008051:Lipid Bilayers; D008081:Liposomes / Q000737:chemistry* / Q000528:radiation effects*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry / Q000528:radiation effects
chemical_list: D007202:Indicators and Reagents; D008051:Lipid Bilayers; D008081:Liposomes; D010743:Phospholipids; D004161:Diphenylhexatriene