Abstract
Different liposomal formulations of Cu,Zn-superoxide dismutase were studied. The effect of lipid composition, initial protein to lipid ratio and type of liposomes on the encapsulation parameters were studied. According to these parameters some liposomal formulations were selected for further tests: dehydration-rehydration vesicles (sDRV) and extruded vesicles (VET) made from PC:Chol:SA and PC:Chol:PI. After encapsulation in these vesicles, no significant loss of enzymatic activity of the enzyme was observed. Pharmacokinetic studies indicated that upon liposomal encapsulation of the enzyme, the terminal half-life of the enzyme after intravenous administration increased 5- to 10-fold. No acute toxicity was observed for the liposomal formulations. The therapeutic activity of the free and liposomal enzyme was assayed in Wistar rats with a chronic inflammation. All liposomal formulations tested showed a reduction of arthritis indexes: 25 to 50% of mean oedema regression was obtained with liposomal enzyme, while no regression with free enzyme and an increase of 50% of the oedema for the control animals were observed.
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