Without a doubt
PEG-SOD has been the
enzyme most studied in PEGylation. One can say that it represents the preferred model to assess chemistries for PEG activation, analytical procedures suitable for conjugate characterization, the influence of PEG size in conjugate removal from circulation and elimination of immunogenicity and antigenicity, and the effect of route of administration. The effect of PEG conjugation was studied in vitro and in vivo models in comparison with the free
enzyme and the following conclusions may be drawn: (1) At the blood vessel level,
PEG-SOD has been shown to provide a greater resistance to
oxidant stress, to improve endothelium relaxation and inhibit
lipid oxidation. (2) In the heart,
PEG-SOD proved to be at least as effective as native SOD in treatment of reperfusion-induced arrhythmias and
myocardial ischemia. (3) In the lung,
PEG-SOD appeared to be able to reduce
oxygen toxicity and E. coli-induced
lung injury, but not in the treatment of lung physiopathology associated with
endotoxin-induced acute
respiratory failure and in the reduction of
asbestos-induced cell damage. (4) On
cerebral ischemia/
reperfusion injuries the effect of
PEG-SOD was uncertain, also due to the difficulty of cerebral cell penetration. (5) In kidney and liver
ischemia both
enzyme forms were found to ameliorate
reperfusion damage. In view of so much positive research on
PEG-SOD, it is surprising that no approved application in human
therapy has been established and approved.