Colloidal suspensions of four biodegradable polymers, polylactic acid (PLA), polybutylcyanoacrylate (PBCA), gelatin (PG) and albumin (PA) were prepared within the size range 1-10 micron. In-vivo biocompatibility tests with synovial tissues were carried out to assess the irritancy of the polymers following intra-articular injection into rabbit knee joints. PLA, PBCA and PG were found to cause joint inflammation whereas PA was well tolerated by the tissues. PA microspheres may provide a means of sustaining the release and reducing the rate of clearance of drugs from the knee joint.

The inflammatory involvement of the synovium in immobilization-induced experimental osteoarthritis in rabbit knees has been investigated. One knee of each of 33 rabbits was immobilized for up to 5 weeks in extension and then allowed to remobilize for up to 8 weeks. Histological examination revealed the presence of marked inflammatory changes in the synovium which were evident after 4 days of immobilization. These were characterized by a rapid proliferation of synovial lining cells followed by mononuclear cell infiltration and fibrosis. The synovial cell proliferation decreased during the latter part of the immobilization period but reappeared in a more severe form during remobilization, at which time gross changes could be demonstrated in the joints. Synovial fluid levels of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase were elevated on day 3 and day 10 but had returned to baseline levels by day 24 of immobilization. Treatment of the animals with the nonsteroidal anti-inflammatory agent flurbiprofen (10 mg/kg/day) had neither a beneficial nor a deleterious effect on any of the parameters measured. This study has shown that immobilization-induced experimental osteoarthritis in rabbits is associated with a marked inflammatory component and that during the remobilization phase of this model the inflammation appears to be a secondary event.

The retention of 131I-labelled albumin microspheres and microsphere-entrapped [131I]rose bengal was investigated in normal and experimentally arthritic knee joints of rabbits. Albumin microspheres were cleared slowly from the joint cavity and no significant difference was observed between normal and inflamed joints. Entrapment of rose bengal within albumin microspheres was found to delay the clearance of the drug from the joint when compared with a solution of rose bengal. In addition, the retention time for entrapped rose bengal was dependent on the degree of inflammation present.

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