Targeted delivery of low-dose dexamethasone using PCL-PEG micelles for effective treatment of rheumatoid arthritis.

Abstract

Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis, but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block-poly (ε-caprolactone) (PCL-PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL-PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL-PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders.

• Authors: Qin Wang, Jiayu Jiang, Wenfei Chen, Hao Jiang, Zhirong Zhang, Xun Sun
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 230 Pg. 64-72 (05 28 2016) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 27057749 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Coumarins
• Interleukin-1beta
• Lactones
• Micelles
• Tumor Necrosis Factor-alpha
• poly(ethylene glycol)-block-poly(epsilon-caprolactone)
• Polyethylene Glycols
• Dexamethasone
• Complement C3a
• coumarin

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Arthritis, Experimental (drug therapy, metabolism, pathology)
• Arthritis, Rheumatoid (drug therapy, metabolism, pathology)
• Cell Survival (drug effects)
• Cells, Cultured
• Complement C3a (metabolism)
• Coumarins (administration & dosage)
• Dexamethasone (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Drug Delivery Systems
• Drug Liberation
• Hindlimb (pathology)
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Interleukin-1beta (metabolism)
• Joints (metabolism, pathology)
• Lactones (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Macrophages (metabolism)
• Mice
• Micelles
• Polyethylene Glycols (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• RAW 264.7 Cells
• Rats, Wistar
• Tumor Necrosis Factor-alpha (metabolism)