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Targeted and Combined TPCA-1-Gold Nanocage Therapy for In Vivo Treatment of Inflammatory Arthritis

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Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that is currently incurable. Inhibition of inflammation can prevent the deterioration of RA. 2-[(Aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) suppresses inflammation via the inhibition of nuclear factor-κ (NF-κB) signaling pathway. Gold-based therapies have been used to treat inflammatory arthritis since the 1940s. Hyaluronic acid (HA) is a targeting ligand for CD44 receptors overexpressed on activated macrophages. Therefore, a combined therapy based on TPCA-1, gold, and HA was explored for the treatment of RA in this study. We used gold nanocages (AuNCs) to load TPCA-1 and modified the TPCA-1 (T) loaded AuNCs with HA and peptides (P) to construct an anti-inflammatory nanoparticle (HA-AuNCs/T/P). An adjuvant-induced arthritis (AIA) mice model was used to investigate the in vivo anti-inflammatory efficacy of HA-AuNCs/T/P. In vivo distribution results showed that HA-AuNCs/T/P had increased and prolonged accumulation at the inflamed paws of AIA mice. Treatment by the HA-AuNCs/T/P suppressed joint swelling and alleviated cartilage and bone damage. By loading to HA-AuNCs/T/P, the effective concentration of TPCA-1 was greatly reduced from 20 to 0.016 mg/kg mice. This study demonstrated that HA-AuNCs/T/P could effectively suppress inflammation and alleviate the symptoms of AIA mice, suggesting a great potential of HA-AuNCs/T/P for the treatment of RA.

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Funding

This research was funded by the China Postdoctoral Science Foundation (2015M582211) and Natural Science Foundation of Henan Province, China (202300410419).

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China

    Ziyi Wang, Jing Yang, Yang Yang, Xiaorong Pu & Nan Zhang

  2. Biotechnology G2018, School of International Education, Henan University of Technology, No. 100 Lianhua Street, Zhengzhou, 450001, China

    Jingnan Zhao

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  1. Ziyi Wang
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Correspondence to Nan Zhang.

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Animal care and experiments were performed with the approval of the animal ethical committee of Zhengzhou University (Zhengzhou, China), according to the requirements of the National Act on the Use of Experimental Animals (China).

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Wang, Z., Yang, J., Yang, Y. et al. Targeted and Combined TPCA-1-Gold Nanocage Therapy for In Vivo Treatment of Inflammatory Arthritis. AAPS PharmSciTech 21, 298 (2020). https://doi.org/10.1208/s12249-020-01856-0

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