Double-blinded, randomized tolerance study of a biologically enhanced Nanogel with endothelin-1 and bradykinin receptor antagonist peptides via intra-articular injection for osteoarthritis treatment in horses.
Authors: Terlinden Antoinette, Jacquet Sandrine, Manivong Seng, Cullier Aurélie, Cassé Frédéric, Legendre Florence, Garcia Araceli Ac, Roullin Gaëlle, Moldovan Florina, Sirois Pierre, Banquy Xavier, Galéra Philippe, Audigié Fabrice, Demoor Magali, Bertoni Lélia
Journal: BMC veterinary research
Summary
# Editorial Summary Osteoarthritis remains a significant cause of lameness and early retirement in performance horses, driving research into targeted intra-articular therapeutics that combine structural support with biological activity. Researchers conducted a double-blinded, randomised safety trial in which eight healthy horses received three injections of a chitosan-hyaluronic acid nanogel engineered to deliver endothelin-1 and bradykinin B1 receptor antagonist peptides into the metacarpophalangeal joint, with contralateral saline injections serving as controls; dosing escalated from standard dose to triple dose over four weeks, with clinical, ultrasonographic and synovial fluid assessment continuing for three months. The nanogel demonstrated acceptable tolerance profiles, with no severe adverse reactions reported, though synovial fluid analysis revealed transient inflammatory markers and cellular responses that returned toward baseline by the three-month endpoint. These findings suggest the delivery system successfully enables prolonged release of bioactive molecules whilst maintaining biocompatibility, potentially offering a dual mechanism of action through both the mechanical properties of the polymer matrix and the anti-inflammatory effects of the peptide antagonists. Further efficacy studies in naturally occurring osteoarthritis are warranted, as this approach could provide a meaningful advancement for managing joint disease in horses where conventional intra-articular treatments have limitations.
Read the full abstract on PubMed
Practical Takeaways
- •This nanogel delivery system shows promise as a potential osteoarthritis treatment option, with demonstrated tolerability in healthy joints at multiple dose levels, though efficacy in diseased joints requires further investigation
- •The drug delivery technology allows prolonged release of bioactive receptor antagonist peptides combined with mechanical support from the polymer matrix, potentially offering dual therapeutic benefits
- •Farriers and veterinarians should monitor for future clinical trial results, as this represents a novel approach to managing equine joint disease that goes beyond traditional corticosteroid or hyaluronic acid injections
Key Findings
- •A functionalized nanogel delivery system with endothelin-1 and bradykinin receptor antagonist peptides was tolerated in healthy equine metacarpophalangeal joints at trial and overdose concentrations
- •Three repeated intra-articular injections at one-week intervals followed by a triple-dose injection at week four showed acceptable safety profile over three months of follow-up
- •Synovial fluid cellular and biochemical parameters, along with ultrasonographic findings, were monitored to assess joint response to the treatment regimen