Development of Intra-Articular Drug Delivery to Alter Progression of Arthritis Following Joint Injury.

摘要

DESIGN: A novel injectable and in situ forming drug depot based on thermally-responsive elastin-like polypeptide (ELP) will be used to deliver an anti-inflammatory drug to an injured joint and provide slow release over time. METHOD(S): Loaded ELP depots were incubated at 37'C with or without 10% serum to quantify in vitro drug release over 1 week. Drug release was quantified by UV-Vis spectroscopy for serum-free conditions and by commercially available ELISA kits (R&D Systems) in the presence of serum. Bioactivity of released sTNFRII was evaluated via the murine L929 cytoprotection assay, an industry standard. DATA ANALYSIS: Means and SEM (n=4) of released drug were calculated at each time point (1, 2, 3, 24, 48, 72, 96, and 168 hours), and data were fit to a nonlinear model of one dimensional steady-state diffusion. FINDINGS: Over 7 days, 80% of IL1Ra was released from the ELP depot in serum-free and serum- containing conditions. For sTNFRII, 8% of loaded drug was released from the ELP depot in serum-free conditions, compared to 79% in the presence of serum. These findings confirm the mechanism that drug is released from the degrading drug depot. Released sTNFRII was found to retain activity against TNF at each time point.