FRI0160 PREPARATION AND PROPERTY OF IGURATIMOD NANOSCALE SUSTAINED-RELEASE SYSTEM

Background Iguratimod, a methanesulfonanilide, has obvious anti-inflammatory function and has been developed exclusively in Asia-Pacific countries. As a novel disease-modifying anti-rheumatic drug, iguratimod is effective in the treatment of RA, but some side effects, such as liver damage and gastrointestinal discomforts are the main concerns in clinical application [1] . Currently, iguratimod is practically insoluble in aqueous solvents and only available in oral dosage forms. The low solubility of drugs leads to incomplete absorption and bioavailability, which affects the clinical efficacy and increases the gastrointestinal side effects of drugs [2]. Objectives In order to improve the bioavailability and alleviate the side effect of gastrointestinal reaction, we changed the dosage form of iguratimod to NanoIguratimod-loaded Hydrogel Composite. Methods Iguratimod nanoparticles (NanoIguratimod) were prepared by using the high-gravity anti-solvent precipitation (HGAP) technique, and its properties were tested. The NanoIguratimod-loaded Hydrogel Composite was prepared and the delivery of the payload was demonstrated. In vitro, the biological effects of NanoIguratimod@Hydrogel on fibroblast-like synoviocytes (RA-FLS) were evaluated. In vivo, the pharmacokinetics of oral raw iguratimod or subcutaneous injection of NanoIguratimod@Hydrogel was carried out in the healthy rats. Further, we evaluated the efficacy of NanoIguratimod@Hydrogel in treating collagen-induced arthritis (CIA) rats. Results By the HGAP technique, we acquired the amorphous form NanoIguratimod with an average size of 295nm, which had higher dissolution rates and higher stability. The release of iguratimod from hydrogel composite in PBS was gradual and sustained for up to 48h compared with NanoIguratimod. NanoIguratimod@Hydrogel inhibited the proliferation, migration, and invasion of RA-FLS in a doses dependent manner. The pharmacokinetic parameters showed better bioavailability and longer half-life time with NanoIguratimod@Hydrogel by subcutaneous administration than oral raw iguratimod. Animal experiments confirmed that subcutaneous injection of NanoIguratimod@Hydrogel (10mg/kg every three days) and oral raw iguratimod (10mg/kg daily) showed similar efficacy in decreasing arthritis index score, pathological score, and expression of cytokines (IL-6, TNF-α and IL-1β). Conclusion Overall, our data suggested that NanoIguratimod@Hydrogel provided new administration routes and extended the administration interval, it may serve as a promising drug delivery approach for the treatment of RA. References [1] Hara M, Abe T, Sugawara S, et al. Long-term safety study of iguratimod in patients with rheumatoid arthritis[J]. Mod Rheumatol., 2007, 17(1):10-16. [2] Zhou T, Ding L, Li X, et al. Determination of iguratimod in rat plasma by high performance liquid chromatography: method and application[J]. Biomed Chromatogr, 2010, 22(3):260-264. Acknowledgement No Disclosure of Interests None declared