N J Zuidam1, S S Lee, D J Crommelin. 1. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), The Netherlands.
Abstract
PURPOSE: 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. CONCLUSION: The degradation of trehalose limits the use of freezing or freeze-drying liposome dispersions as a way to minimise irradiation damage.
PURPOSE: 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. CONCLUSION: The degradation of trehalose limits the use of freezing or freeze-drying liposome dispersions as a way to minimise irradiation damage.
Authors: C Brassinne; G Atassi; J Frühling; W Penasse; A Coune; J Hildebrand; J M Ruysschaert; C Laduron Journal: J Natl Cancer Inst Date: 1983-06 Impact factor: 13.506
Authors: A Coune; J P Sculier; J Frühling; P Stryckmans; C Brassinne; G Ghanem; C Laduron; G Atassi; J M Ruysschaert; J Hildebrand Journal: Cancer Treat Rep Date: 1983-11