Glucocortlcoid-Loaded Core-Cross-Linked Polymeric Micelles with Tailorable Release Kinetics for Targeted Therapy of Rheumatoid Arthritis

摘要

Glucocorticoids (GCs) play a prominent role in the therapeutic management of rheumatoid arthritis (RA) and other chronic inflammatory diseases. However, the occurrence of significant adverse effects, especially when high doses are required, forms an important limitation with respect to the clinical apphcation of GCs. Targeted delivery strategies for improving the accumulation of GCs in the target tissue have therefore attracted considerable attention in recent years, especially for RA therapy. In RA, such strategies commonly exploit the up to 40-fold increase in the permeability of the blood-joint barrier of the inflamed synovium for macro-molecules and nanoparticulates. This preferred distribution of systemically administered nanomedicines to arthritic joints enables the inflammation-directed targeting of GCs, thereby improving efficacy and reducing systemic GC toxicity.