Liposomal clodronate eliminates synovial macrophages, reduces inflammation and ameliorates joint destruction in antigen-induced arthritis.
OBJECTIVE
To investigate the efficacy of a single i.v. dose of clodronate encapsulated within small unilamellar vesicles in suppressing joint inflammation and the histological progression of rat antigen-induced arthritis (AIA).


METHODS
Rats with AIA received a single i.v. injection of 20 mg of clodronate encapsulated within small unilamellar vesicles (SUVc) or larger multilamellar vesicles (MLVc) 7 days post-arthritis induction. Free clodronate or saline were used as negative controls.


RESULTS
SUVc was shown to be more effective than MLVc, sustaining a significant reduction in knee swelling for up to 7 days after the initial systemic administration. Knee swelling in free clodronate-treated animals was not significantly affected. The increased efficacy of SUVc in reducing inflammation and joint destruction was associated with a significant depletion of resident ED1+, ED2+ and ED3+ macrophages from the synovial membrane (SM).


CONCLUSIONS
SUVc is more efficient than MLVc in reducing the severity of inflammation and joint destruction in rat AIA, and is associated with the specific elimination of macrophage subpopulations from the SM.
Richards
P J
PJ
Rheumatology Research Laboratory, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Williams
A S
AS
Goodfellow
R M
RM
Williams
B D
BD
D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D004002:Clodronic Acid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004337:Drug Carriers; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D008297:Male; D012157:Mononuclear Phagocyte System / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013583:Synovial Membrane / Q000187:drug effects* / Q000473:pathology
D018712:Analgesics, Non-Narcotic; D004337:Drug Carriers; D008081:Liposomes; D004002:Clodronic Acid