| Summary: | 碩士 === 國立暨南國際大學 === 應用化學系 === 97 === In the present study, we developed hyaluronan modified uricases (HA-uricase) for gout therapy. Smaller sized HA-uricases, formation after their decomposition in the joints, were able to get into articular cartilage to dissolve the deposited urate crystals. Hyluronans were firstly fragmented to varied sizes by acid digestions. The effects of these hyaluronans with different molecular weights were then examined on elicited inflammation and their biodistribution. Results indicated that hyaluronans with lower molecular weights (8.6x10^3Da) induced significant inflammatory responses, whereas hyaluronans with higher molecular weights (1.1x10^6Da) did not. The fluorescent dye (5-AMF)-labeled hyaluronans remained in the joints for at least 4 days, and were able to reach to articular cartilage. The activity of hyaluronan modified uricase was around 64.83%, which could efficiently dissolve monosodium urate (MSU) crystals and reduce the inflammation induced by them. Taken together, the HA-uricases can dissolve urate crystals in the joints, and likely in articular cartilage. This ability makes HA-uricases a potential strategy for gout therapy, especially for the urate crystals deposited in articular cartilage.
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