Long term safety and efficacy of a functionalized nanogel with endothelin-1 and bradykinin receptor antagonist peptides for treatment of osteoarthritis of the metacarpophalangeal and distal interphalangeal joints in horses: a descriptive clinical pilot study.

Abstract

BACKGROUND: Intra-articular drug delivery systems (DDS) are emerging as promising therapies for osteoarthritis (OA), yet their efficacy in spontaneous clinical cases remains largely untested. This uncontrolled, descriptive pilot study was designed to provide a proof of concept for the feasibility, safety, and preliminary clinical effects of intra-articular administration in sport horses with naturally occurring OA. The study involved a peptide-functionalized nanogel composed of chitosan and hyaluronic acid, delivering endothelin type A (BQ-123) and bradykinin B1 (R-954) receptor antagonists, which have previously demonstrated anti-inflammatory and chondroprotective properties in preclinical models. RESULTS: Eight client-owned sport horses with moderate OA of the metacarpophalangeal (MCPJ) or distal interphalangeal joint (DIPJ) received a single intra-articular injection of 2.4 mL nanogel and were followed for 12 months. No major adverse events were observed. Two horses developed mild, transient joint swelling that resolved within three days. Seven of eight horses showed improvement in lameness scores by week 12, although complete resolution on hard ground circles was observed in only two horses. All horses were sound on soft ground and returned to competition, with a median time of 128 days post-treatment. Six horses remained in active competition at one year without additional intervention. Four horses (50%) met the predefined primary outcome of return to the same level and frequency of competition as before lameness onset. Horses treated for DIPJ OA and those showing radiographic joint space narrowing were overrepresented among treatment failures. CONCLUSIONS: Intra-articular administration of a peptide-functionalized nanogel was feasible and well tolerated in sport horses with naturally occurring OA and was associated with partial but prolonged clinical improvement. Although only half of the horses achieved full return to pre-lameness performance, most showed sustained clinical benefit without additional treatment over one year. These findings support further investigation of this drug delivery system in larger, randomized controlled trials to better define its therapeutic efficacy and optimal indications.