Therapeutic activity and biodistribution of a nano-sized polymer-dexamethasone conjugate intended for the targeted treatment of rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory autoimmune disease caused by alteration of the immune system. Current therapies have several limitations and the use of nanomedicines represents a promising strategy to overcome them. By employing a mouse model of adjuvant induced arthritis, we aimed to evaluate the biodistribution and therapeutic effects of glucocorticoid dexamethasone conjugated to a nanocarrier based on biocompatible N -(2-hydroxypropyl) methacrylamide copolymers. We observed an increased accumulation of dexamethasone polymer nanomedicines in the arthritic mouse paw using non-invasive fluorescent in vivo imaging and confirmed it by the analysis of tissue homogenates. The dexamethasone conjugate exhibited a dose-dependent healing effect on arthritis and an improved therapeutic outcome compared to free dexamethasone. Particularly, significant reduction of accumulation of RA mediator RANKL was observed. Overall, our data suggest that the conjugation of dexamethasone to a polymer nanocarrier by means of stimuli-sensitive spacer is suitable strategy for improving rheumatoid arthritis therapy. A mouse model of adjuvant induced arthritis was used to evaluate the anti-inflammatory therapeutic effects of N -(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based nanomedicines conjugated with dexamethasone. Intravenously- or intraperitoneally-administered HPMA-dexametasone conjugates accumulated in arthritic paws. Dexamethasone is released from the HPMA carrier in the slightly acidic environment of the arthritic paw and phagocytosed by resident activated macrophages where the rest of dexamethasone is released due to acidic nature in phagolysosome. The treatment with the conjugate decreased the clinical severity and level of RANKL in the arthritic paws. [Display omitted] • N -(2-hydroxypropyl) methacrylamide copolymer was conjugated with dexamethasone (HPMA-DEX). • HPMA-DEX accumulates specifically in the arthritic paws of mice. • Treatment with HPMA-DEX reduces the clinical severity of acute arthritis in mice. • Comparison of HPMA-DEX and free DEX shows improved therapeutic effect of HPMA-DEX. [ABSTRACT FROM AUTHOR]