Scintigraphic imaging of radiolabelled drug delivery systems in rabbits with arthritis

This paper describes a novel approach for designing drug delivery systems for intra-articular (i.a.) treatment of rheumatoid arthritis. Retention of these systems was evaluated by radiolabeling with Tc-99m and gamma scintigraphy in arthritic rabbits. Liposome, niosome, lipogelosome and niogelosome formulations of Diclofenac Sodium (DFNa) have been prepared and drug release properties and in vitro characterisation studies have been carried out. According to characterisation results L1 (DMPC: CHOL DCP (7:1:2)), L1J1 (DMPC: CHOL DCP (7:1:2) in C-940 1:1 (w/w)), N (SUR I: CHOL: DCP (7:1:2)) and NJ1 (SUR I: CHOL: DCP (7:1:2) in C-940 1:1 (w/w)) formulations were chosen for the further studies. Retention time of these formulations was evaluated by gamma scintigraphic imaging studies. Rabbits with antigen-induced arthritis were injected intra-articularly with Tc-99m labelled drug delivery systems. Serial scintigraphic images were obtained to investigate the retentions of labelled drug delivery systems in the arthritic joints and choose a suitable formulation for the treatment protocol of arthritis. At the end of the scintigraphic imaging studies it was observed that radiolabelled lipogelosome formulation containing DFNa (L1J1) retained much longer in the experimentally arthritic knee joints of the rabbits. This formulation was used for the treatment protocol of arthritis. Mono articular arthritis was induced in the knee joints of rabbits and it was monitored at regular time intervals by measuring changes in knee joint diameter. Also macroscopic and histopathologic evaluations were performed for further evaluation of arthritis. Great retention of DFNa in the arthritic joint might reduce potential adverse systemic effects of the drug because of local administration into the diseased area. It appeared to be a promising drug delivery system for intra-articular drug delivery. (C) 2005 Elsevier B.V. All rights reserved.