ArticlePharmaceutical research2025
Enhanced Penetration and Retention of an Antibody in the Articular Cartilage Through Aggrecan Binding and Molecular Downsizing.
Article in Pharmaceutical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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11 authors.
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Abstract
purposeDelivering immunogloblin G (IgG) to the articular cartilage is a challenge and presents an obstacle in developing therapeutic antibodies for articular diseases. In this study, we focused on binding to the aggrecan-a key component of the cartilage matrix as a proteoglycan-and molecular downsizing to enhance the penetration and retention of antibodies in the articular cartilage.
methodsThe control IgG (143 kDa), anti-aggrecan IgG (141 kDa), F(ab')2 (93.0 kDa), and Fab (44.9 kDa) were intra-articularly injected into a rabbit joint, and the concentrations of each molecule in synovial fluid, articular cartilage, and plasma were monitored.
resultsEach molecule exhibited a similar elimination profile in synovial fluid. However, compared to the control IgG, anti-aggrecan IgG showed increased exposure in cartilage. Moreover, anti-aggrecan F(ab')2 exhibited even higher concentrations in cartilage, while the anti-aggrecan Fab demonstrated the highest and most long-lasting concentration profile in cartilage. Fluorescence imaging of the ex vivo cartilage penetration further supported the superior transport of the anti-aggrecan Fab and F(ab')2 compared to the control IgG and the anti-aggrecan IgG.
conclusionsOur study demonstrates that binding to the cartilage matrix, in addition to molecular size, is important, and that their combination has a synergistic effect on the antibody exposure in the articular cartilage.
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