Related Experiment Video
Updated: Mar 25, 2026
Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
Published on: April 7, 2023
Engineered Protein Nanoparticles Enable Targeted Topical Delivery of Upadacitinib for Enhanced Arthritis Therapy
Wenrui Zhang1,2, Chaonan Jin3, Chao Ma3
1Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
Abstract:
Rheumatoid arthritis (RA) is a chronic autoimmune disorder driven by persistent synovial inflammation and leading to joint destruction. Although the Janus kinase (JAK) inhibitor upadacitinib (UPA) is clinically effective, its systemic administration is associated with dose-limiting toxicities and poor patient adherence, highlighting an urgent need to minimize systemic exposure. Topical application offers a promising route for targeted joint delivery, but its efficacy is hampered by the formidable skin barrier and the poor retention of conventional formulations. To overcome these challenges, we developed a protein-based nanoparticle system by assembling engineered protein K72 with carboxylate-terminated poly(ethylene glycol) (PEG-COOH) to encapsulate UPA. This design significantly enhanced nanoparticle stability, drug loading capacity, and transdermal penetration efficiency. The engineered nanoparticles demonstrated sustained drug release and superior skin penetration. In a collagen-induced arthritis (CIA) mouse model, topical application of these nanoparticles achieved pronounced therapeutic efficacy against RA progression, with no observable systemic toxicity. This work establishes a safe, convenient, and highly effective topical nanoplatform for the local management of RA.
Insights
Engineered nanoparticles deliver rheumatoid arthritis drug topically, enhancing joint treatment and reducing systemic exposure. This novel nanoplatform offers a safer, more effective approach for managing rheumatoid arthritis (RA).
Area of Science:
- Biomaterials Science
- Nanotechnology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint inflammation and destruction.
- Current treatments like upadacitinib (UPA) have systemic toxicities and adherence issues.
- Targeted topical delivery faces challenges from the skin barrier and poor drug retention.
Purpose of the Study:
- To develop a novel nanoparticle system for effective topical delivery of upadacitinib (UPA) for rheumatoid arthritis (RA).
- To overcome the limitations of conventional topical formulations and systemic drug administration.
Main Methods:
- Engineered protein K72 was assembled with poly(ethylene glycol) (PEG-COOH) to create a protein-based nanoparticle system encapsulating UPA.
- Nanoparticle stability, drug loading, and transdermal penetration were evaluated.
- Therapeutic efficacy and systemic toxicity were assessed in a collagen-induced arthritis (CIA) mouse model.
Main Results:
- The engineered nanoparticles exhibited enhanced stability, drug loading capacity, and transdermal penetration.
- Sustained drug release and superior skin penetration were observed.
- Topical nanoparticle application demonstrated significant therapeutic efficacy in the CIA mouse model with no systemic toxicity.
Conclusions:
- A safe, convenient, and effective topical nanoplatform for local RA management was successfully developed.
- This approach minimizes systemic exposure to UPA, addressing key limitations of current therapies.
- The protein-based nanoparticle system shows promise for targeted treatment of joint diseases.
More Related Videos
Related Concept Videos
01:24Site-Targeted Drug Delivery Systems: Polymeric Carriers
01:24Modified-Release Drug Delivery Systems: Site-Targeted