Zyn-Linker delivery of antirheumatic agents

Area of Science:

• Biomedical Engineering
• Radiopharmaceutical Chemistry
• Rheumatology

Background:

• Systemic medications are insufficient for managing refractory rheumatoid arthritis joints.
• Local administration of aggressive therapy is required for a substantial number of patients.
• Novel drug delivery systems are needed to enhance localized therapeutic efficacy.

Purpose of the Study:

• To evaluate Zyn-Linkers as a novel drug delivery system for intra-articular therapeutics.
• To assess the localization and retention of Zyn-Linkers within the joint.
• To determine the potential of Yttrium-90 (Y-90) Zyn-Linker as a radiation synovectomy agent.

Main Methods:

• Intra-articular injection of Zyn-Linkers (containing Re-186 or Y-90) into rabbit knee joints.
• Whole-body imaging and biodistribution studies to assess localization and retention.
• Calculation of therapeutic doses and safety profiles based on extrapolated human data.

Main Results:

• Zyn-Linkers rapidly and homogenously bound to synovial lining cells.
• Re-186 and Y-90 Zyn-Linkers demonstrated excellent localization (>90% in knee) for 4-6 days post-injection.
• Calculated Y-90 Zyn-Linker dose for effective synovium radiation (8,000 cGy) is comparable to existing agents, with a favorable predicted safety profile.

Conclusions:

• Zyn-Linkers exhibit desirable localization and retention properties for intra-articular drug delivery.
• Y-90 Zyn-Linker shows potential as a safe and effective radiation synovectomy agent.
• Zyn-Linkers can be engineered for controlled drug release, offering a dual-action approach for refractory arthritis management.