An Agarose–Curdlan Nanogel that Carries Etanercept to Target and Neutralises TNF-α Produced by Dectin-1-Expressing Immune Cells

Etanercept (ETA) has been used as a drug to neutralise tumour necrotic factor alpha (TNF-α) for treatment of rheumatoid arthritis (RA), yet there are limitations concerning its low specific drug targeting and side effects. In this study, agarose–curdlan encapsulating etanercept (ACE) gel was successfully formulated and evenly distributed as nano-particles of 30–100 nm diameter, exhibiting an ETA encapsulation efficiency of 73.8% and an ETA-releasing efficiency of 50% after 52 h. The number of dectin-1-overexpressing macrophage cells, RAW264.7, exposed to ACE that migrated in the Boyden chamber assay was equal to that exposed to either agarose–curdlan or curdlan nanogels, but substantially higher than those exposed to agarose gel and water-soluble ETA by 67 and 141 fold, respectively ( p < 0.05), suggesting the targeting effect of curdlan on dectin-1. Enzyme-linked immunosorbent assay revealed that the ETA released from the ACE nanogel could neutralise TNF-α secreted by lipopolysaccharide (LPS)-induced RAW264.7. Moreover, at 24 h and 72 h, the released ETA showed 1.3- to 4.4-fold greater effectiveness, respectively, than water-soluble ETA. This study demonstrates that the ACE nanogel can attract immune cells and slowly release ETA to efficiently neutralise the TNF-α produced by these cells and, thus, could be a promising ETA carrier for targeted RA treatment.