Targeted delivery of hyaluronic acid-coated solid lipid nanoparticles for rheumatoid arthritis therapy

Meiling Zhou,Jierong Hou,Zhirong Zhong,Na Hao,Yan Lin,Chunhong Li

doi:10.1080/10717544.2018.1447050

Abstract

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Long-term, high-dose glucocorticoid therapy can be used to treat the disease, but the fact that the drug distributes systemically can give rise to severe adverse effects. Here we develop a targeted system for treating RA in which the glucocorticoid prednisolone (PD) is encapsulated within solid lipid nanoparticles (SLNs) coated with hyaluronic acid (HA), giving rise to HA-SLNs/PD. HA binds to hyaluronic receptor CD44, which is over-expressed on the surface of synovial lymphocytes, macrophages and fibroblasts in inflamed joints in RA. As predicted, HA-SLNs/PD particles accumulated in affected joint tissue after intravenous injection into mice with collagen-induced arthritis (CIA), and HA-SLNs/PD persisted longer in circulation and preserved bone and cartilage better than free drug or drug encapsulated in SLNs without HA. HA-SLNs/PD reduced joint swelling, bone erosion and levels of inflammatory cytokines in serum. These results suggest that encapsulating glucocorticoids such as PD in HA-coated SLNs may render them safe and effective for treating inflammatory disorders.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that results in systemic autoimmune destruction of bone and cartilage
The results showed that the uptake of hyaluronic acid (HA)-solid lipid nanoparticles (SLNs)/PD was much higher than SLNs/PD when the RAW264.7 cells were activated with LPS
In order to reduce the need for long-term, high-dose systemic glucocorticoid therapy in RA (Baschant et al, 2012; Krasselt & Baerwald, 2014), we developed SLNs coated with hyaluronic acid that can persist in the circulation and

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that results in systemic autoimmune destruction of bone and cartilage. Glucocorticoids are widely used to manage this disease as well as other chronic inflammatory diseases (Smolen & Steiner, 2003) These drugs distribute systemically in the body, necessitating the use of sustained high-dose therapy, which often leads to severe side effects, such as muscle weakness, increased risk of infection, growth retardation, and peptic ulcer disease (Yuan et al, 2012). By packaging glucocorticoids into liposomes, nanoparticles, micelles, nanoemulsions, or SLNs could enhance drug accumulation preferentially at target sites (Crielaard et al, 2012). Among these packaging systems, SLNs are attractive because of their good biocompatibility, high drug loading capacity, excellent physical stability, and ability to protect labile drugs from degradation (Wissing et al, 2004).

Methods

Results

Conclusion