Neutrophil-Mediated Drug Delivery Nanoplatform Constructed from Celastrol Loaded Liposome for Targeted Therapy of Rheumatoid Arthritis.

Abstract

Rheumatoid arthritis (RA) may lead to irreversible joint damage, seriously affecting the health of patients. Cell-mediated drug delivery strategies provide a significant promise for improving drug delivery efficiency and enhancing therapeutic efficacy in RA. Herein, a neutrophil-mediated nanoplatform, constructed from celastrol-loaded liposome (LP-Cel) and neutrophils (NEs) on the outer surface capable of inflammation migration ability, namely, NEs-LP-Cel, is developed for RA treatment. By exploiting the inflammatory environment of RA and the inflammatory chemotaxis of neutrophils, LP-Cel is transported to inflamed tissues to release celastrol and display anti-inflammatory effects. Experimental results demonstrate that NEs-LP-Cel can effectively accumulate at the inflammation sites, reduce paw swelling, and decrease the expression of inflammatory factors (TNF-α and IL-1β) in joint tissues of RA rats, indicating enhanced therapeutic effects and negligible side effects, providing a new way for using neutrophil-mediated nanocarriers as delivery nanoplatforms to achieve treatment in inflammatory diseases.