Title:A Novel Etanercept-loaded Nano-emulsion for Targeted Treatment of
Inflammatory Arthritis via Draining Lymph Node
Volume: 21
Issue: 8
Author(s): Chenglong Li*, Guanting lu, Yue Jiang, Huaiyu Su*Chen Li*
Affiliation:
- Department of Pharmacy, Deyang People’s Hospital, Deyang 618000, China
- Department of Pharmacy, Deyang People’s Hospital, Deyang 618000, China
- Centre for Translational Research in
Cancer, Sichuan Cancer Hospital & Institute, Chengdu 610000, China
- School of Medicine, University of Electronic
Science and Technology, Chengdu 610000, China
Keywords:
Rheumatoid arthritis, draining lymph nodes, etanercept-loaded nano-emulsion, TNF-α, inflammatory arthritis, targeted treatment.
Abstract:
Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the
global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no
known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor
on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic
distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant
role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune
response and inflammatory cytokine production.
Aim: The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions
(NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared
by high-pressure homogenization method and modified with DSPE-mPEG2000 and Ca(OH)2.
Methods: A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To
decrease aggregation and load EN, DSPE-mPEG2000 and Ca(OH)2 were successively decorated on the
surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were
investigated by using a laser particle size analyzer and transmission electron microscopy, respectively.
The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation.
In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development
of the mouse arthritis model.
Results: Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had
no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA)
mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as,
anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic
score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory
cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN.
Conclusion: NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work
provides an experimental foundation for expanding the clinical application of EN.
