Biofunctionalized Liposomes to Monitor Rheumatoid Arthritis Regression Stimulated by Interleukin-23 Neutralization.
Ana Cláudia LimaCláudia F CamposCristina CunhaAgostinho CarvalhoRui Luis ReisHelena FerreiraNuno M NevesPublished in: Advanced healthcare materials (2020)
Even after the revolution of rheumatoid arthritis (RA) treatment with biologic agents, this debilitating disease remains a major clinical problem. The outstanding outcomes of the systemic administration of antibodies (Abs) are narrowed by the risk of serious side effects and limited efficacy due to their short half-life. Interleukin-23 (IL-23) is a crucial pro-inflammatory cytokine involved in inflammation that potently enhances the generation of T-helper type-17 (Th17) cells. Hence, in this work, anti-IL-23 Abs are immobilized at the surface of liposomes to increase their therapeutic efficacy, being gold nanoparticles (AuNPs) incorporated to allow monitoring the biodistribution of the liposomes after systemic administration as well as due to their anti-inflammatory and antioxidant effects. A stable monodispersed liposomes' suspension with around 130 nm is produced and efficiently biofunctionalized with anti-IL-23 Abs. IL-23 capture and neutralization capacity are confirmed using activated macrophages. Biological assays demonstrate their hemocompatibility and cytocompatibility with human articular chondrocytes, macrophages, and endothelial cells. Moreover, the neutralization of IL-23 by the biofunctionalized liposomes efficiently decreases the production of IL-17A by peripheral blood mononuclear cells of healthy donors and RA patients who are activated to Th17 differentiation. Therefore, the developed formulation may be a promising strategy to treat RA.
Keyphrases
- rheumatoid arthritis
- drug delivery
- endothelial cells
- disease activity
- gold nanoparticles
- drug release
- end stage renal disease
- anti inflammatory
- oxidative stress
- interstitial lung disease
- chronic kidney disease
- ejection fraction
- induced apoptosis
- immune response
- computed tomography
- photodynamic therapy
- peritoneal dialysis
- systemic sclerosis
- insulin resistance
- endoplasmic reticulum stress
- drug induced
- idiopathic pulmonary fibrosis
- glycemic control
- pet imaging
- high glucose