The arthrotropism of macromolecules in adjuvant-induced arthritis rat model: a preliminary study.
OBJECTIVE
To study the accumulation of macromolecules into the arthritic joints and the possible applications of such phenomenon.


METHODS
The accumulation of plasma albumin in the joints of adjuvant-induced arthritis (AIA) rat model was first visualized with Evans blue injection. A N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer contrast agent was then synthesized and injected into the AIA rats to allow qualitative examination of biodistribution and pharmacokinetics of the injected macromolecule with magnetic resonance imaging (MRI). Vital organs and the diseased joints were isolated and examined histologically to correlate with the MRI findings.


RESULTS
Deep blue color developed around the arthritic joints of the AIA rat a few hours after the injection of Evans blue. MR imaging of the AIA rats injected with polymer contrast agent demonstrated a gradual but very strong accumulation of the injected polymer in the arthritic joints, which lasted for 1-2 days. Observed differences in the concentration of the injected polymer in the joints correlated with disease severity as assessed histologically.


CONCLUSIONS
Profound arthrotropism of macromolecules in the AIA rat model was demonstrated with various imaging tools. These observations should help in the conceptual and practical design of novel macromolecular delivery systems for the imaging and treatment of rheumatoid arthritis.
Wang
Dong
D
Department of Pharmaceutics & Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA. dong.wang@m.cc.utah.edu
Miller
Scott C
SC
Sima
Monika
M
Parker
Dennis
D
Buswell
Henry
H
Goodrich
K Craig
KC
Kopecková
Pavla
P
Kopecek
Jindrich
J
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D003287:Contrast Media; D005070:Evans Blue; D006571:Heterocyclic Compounds; D007091:Image Processing, Computer-Assisted; D007596:Joints / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008689:Methacrylates / Q000493:pharmacokinetics*; D008970:Molecular Weight; D009942:Organometallic Compounds; D011108:Polymers; D051381:Rats; D011917:Rats, Inbred Lew; D012709:Serum Albumin / Q000378:metabolism; D014018:Tissue Distribution
D003287:Contrast Media; D006571:Heterocyclic Compounds; D008689:Methacrylates; D009942:Organometallic Compounds; D011108:Polymers; D012709:Serum Albumin; D005070:Evans Blue; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; C032802:hydroxypropyl methacrylate