Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

Abstract

Background: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration and serious adverse reactions during long-term administration. To achieve better treatment and reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system. Results: The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was -22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo biodistribution experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility.Conclusion: The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.

Update on Nanoparticle-Based Drug Delivery System for Anti-inflammatory Treatment

“…Exosomes are 30–100 nm natural nanovesicles secreted by various cell types, such as tumor cells, mesenchymal stem cells, and immune cells. Exosomes are good carriers with low cytotoxicity, non-immunogenicity, and endogenous properties ( Yan et al, 2020 ). Recently, exosome-based drug delivery systems have been studied, and it is worth noting that exosomes have a natural targeting property because of the native biological functions of the original cells, which may benefit disease treatment ( Wu et al, 2020 ).…”

“…They selected hexyl 5-aminolevulinate hydrochloride (HAL) to obtain HAL-containing M2 exosome (HAL@M2 Exo) and found that HAL@M2 Exo had excellent inflammation-tropism capability, as both in vitro and in vivo experiments demonstrated anti-inflammatory effects in atherosclerosis. Yan et al (2020) used exosome as carrier, encapsulating dexamethasone sodium phosphate, modified the surface with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol), in vitro study, the FPC-Exo/Dex drug delivery system showed anti-inflammatory effect against RAW264.7 cells.…”

Nerve growth factor loaded macrophage-derived nanovesicles for inhibiting neuronal apoptosis after spinal cord injury

“…To evaluate the cytotoxicity of 5-25 mg/ml blank NVs to PC12 cells, MTT analysis was performed. 30 PC12 cells were seeded in 96-well plates at a density of 1 Â 10 4 cells per well. After the cells adhered to the wall, NGF-NVs were diluted with culture medium to concentrations of 5, 10, 15, 20 and 25 mg/mL.…”

Exosomes as Drug Delivery Systems: Endogenous Nanovehicles for Treatment of Systemic Lupus Erythematosus

“…Currently, GCs are the most effective anti-inflammatory drugs available for SLE [ 6 ], but clinical application is limited by their nonspecific distribution after systemic administration and serious adverse reactions during long-term administration. A recent study by Yan et al provides a promising strategy using exosomes as nanocarriers to enhance the therapeutic effect of GCs against RA [ 227 ], establishing a biomimetic exosome encapsulating dexamethasone sodium phosphate nanoparticle, whose surface was modified with folic acid (FA)-PEG-cholesterol (Chol) compound.…”