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Gamma-Irradiation of Non-Frozen, Frozen, and Freeze-Dried Liposomes

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Abstract

Purpose. The aim of this work was to investigate the possibilities and limitations of gamma-irradiation as a sterilisation method for non-frozen, frozen, and freeze-dried liposomes.

Methods. Liposomes with an average size of 0.2 µm were irradiated with doses up to about 5 × 104 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 (non-frozen, 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.

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Authors and Affiliations

  1. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), participant in Groningen Utrecht Institute for Drug Exploration (GUIDE), Faculty of Pharmacy, Utrecht University, Utrecht, The Netherlands

    Nicolaas J. Zuidam, Stephen S. L. Lee & Daan J. A. Crommelin

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  1. Nicolaas J. Zuidam
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  2. Stephen S. L. Lee
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  3. Daan J. A. Crommelin
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Zuidam, N.J., Lee, S.S.L. & Crommelin, D.J.A. Gamma-Irradiation of Non-Frozen, Frozen, and Freeze-Dried Liposomes. Pharm Res 12, 1761–1768 (1995). https://doi.org/10.1023/A:1016282109566

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