초록 |
We prepared the hyaluronic acid-based nanoconjugates with methotrexate (MTX), a well-known drug to treat cancer and rheumatoid arthritis (RA). Hyaluronic acid (HA) has a great binding affinity to CD44 (HA receptor) which is over-expressed at the inflammatory disease site. We investigated the potential of HA-MTX nanoconjugate for targeted drug delivery to the RA site. The nanoconjugates were accumulated in the inflamed site via HA-CD44 binding. In the mildly acidic condition of the inflammatory site, the ester linkage of HA-MTX was cleaved by hydrolysis, resulting in release of MTX. We also observed that HA-MTX was effectively taken up by activated macrophages cells, responsible for inflammation. Additionally, in vivo experimental result demonstrated its clinical performance to the inflamed joint in collagen-induced arthritis mice model. These results suggest that HA-MTX has a potential as an anti-inflammatory drug for RA treatment. |