Uptake of verteporfin by articular tissues following systemic and intra-articular administration.
Photodynamic therapy (PDT) using the photosensitizer BPD-Verteporfin (liposomal benzoporphyrin derivative-monoacid ring A) has been shown in previous studies to be effective in the amelioration of inflammatory arthritis in both the MRL-lpr mouse and the New Zealand White (NZW) rabbit models, and could potentially offer alleviation of certain inflammation-related symptoms of rheumatoid arthritis. Time and dose dependency of BPD-MA tissue uptake was carried out in the inflamed synovium and other articular and peri-articular tissues following intravenous and intra-articular administration in the NZW rabbit model. As some articular and peri-articular tissues are difficult to extract, this study uses a rapid fluorimetric sampling of tissues following dissolution in Soluene 350. Our results showed that i.v. injected BPD-MA preferentially distributed in the inflamed synovium, and in tissues with a high degree of vascularization. Little or no association was found with avascular tissues such as cartilage and tendons. Clearance from the synovium was rapid, supporting earlier rather than late light treatment. Much higher association of BPD-MA with the synovium was achieved using intra-articular injection, and BPD-MA concentrations were maintained at relatively steady levels for several hours. These observations support the possibility that PDT could offer a safe, highly versatile clinical option for the management of inflamed joints in autoimmune disorders.
Chowdhary
R K
RK
Department of Microbiology, University of British Columbia, Vancouver, Canada. rchowdha@qlt-pdt.com
Ratkay
L G
LG
Canaan
A J
AJ
Waterfield
J D
JD
Richter
A M
AM
Levy
J G
JG
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001168:Arthritis / Q000139:chemically induced / Q000378:metabolism; D007270:Injections, Intra-Articular; D007275:Injections, Intravenous; D008081:Liposomes; D010047:Ovalbumin; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D013582:Synovial Fluid / Q000378:metabolism*; D014018:Tissue Distribution; D000077362:Verteporfin
D000970:Antineoplastic Agents; D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D010047:Ovalbumin