Superoxide dismutase entrapped in long-circulating liposomes: formulation design and therapeutic activity in rat adjuvant arthritis

The aim of this study was to investigate whether long-circulating liposomes can improve the anti-inflammatory activity of superoxide dismutase (SOD). Small-sized poly(ethyleneglycol) (PEG)-liposomes containing SOD were prepared via different preparation protocols and characterized in terms of encapsulation efficiency (EE), size, enzymatic activity and protein structure, to establish conditions where high EE can be combined with preservation of enzyme activity, and structure. It was observed that structural information from circular dichroism analyses does not correlate with data on enzyme activity. SOD-containing PEG-liposomes prepared by the dehydration-rehydration method appeared o represent the most attractive formulation for in vivo evaluation. The therapeutic potential of selected SOD-containing PEG-liposomes was established and compared with SOD entrapped in stearylamine (SA)-liposomes and `free' SOD upon intravenous (i.v.) injection in an arthritic rat model. Both small PEG-liposomes and SA-liposomes showed a superior therapeutic activity compared to `free' SOD, with PEG-liposomes inducing stronger anti-inflammatory effects than SA-liposomes. (C) 2002 Elsevier Science B.V. All rights reserved.