Studies Upon the Toxicity of Polyethylene Glycol Coated Lipid Vesicles: Acute Hemodynamic Effects, Pyrogenicity and Complement Activation

Abstract

The toxicity of PEG-coated liposomes has been examined by testing the ability of such vesicles to (a) initiate a fever response, (b) activate complement and (c) alter various hemodynamic parameters in rabbits. The results indicate that DSPC/Chol/DMPG/Vit.E/ PE-PEG (45.5:40:9:1:4.5) vesicles injected I.V. in rabbits at a lipid dose of ∼4 μmole/kg do not elicit a fever response either due to the presence of bacterial contamination, or by activating the release of endogenous pyrogens and, in addition, cause no statistically significant (Mann-Whitney p >0.05) changes in various hemodynamic parameters compared to injection of saline. An in-vitro hemolytic assay indicated that these same vesicles cause no activation of complement over the lipid concentration range 0.06–64 mM. These results are discussed in terms of the potential use of PEG-coated vesicles as blood pool imaging agents in nuclear medicine.

Keywords::

• Toxicity
• Polyethylene glycol
• Hemodynamic
• Pyrogen
• Complement