Monitoring the effect of PEGylation on polyethylenimine in vivo using nuclear imaging technique.

Polyethyleneimine (PEI) has been extensively investigated for use as a nonviral gene delivery vector due to its "proton sponge" mechanism. This work monitored the effect of PEGylation in vivo using nuclear imaging technique. We synthesized galactosylated PEI-PEG with different levels of PEG substitution ranging from 4.1 to 13.3 mol% of PEI amino groups. Validation of the differences of the in vivo distribution in the varying degrees of PEG substitution was performed using nuclear imaging with a gamma camera. PEGylated PEIs could easily label with reduced 99mTc because of their interaction with PEI amino groups. After systemic administration of 99mTc PEGylated Gal-PEIs, rapid accumulation in the liver, spleen, and lung was observed. However, with increasing amounts of PEG, the lung uptake was markedly reduced. These results demonstrate that nuclear imaging technique may be used as a basic screening tool for determining the optimized system of PEGylated Gal-PEIs. Once optimized, this system could be used as a hepatocyte targeted non-viral gene delivery vector which minimizes unspecific interactions with cellular blood components such as vessel endothelia and plasma proteins. Copyright 2004 Elsevier Inc.