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BMC veterinary research2024; 20(1); 547; doi: 10.1186/s12917-024-04352-w

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.

Abstract: Osteoarthritis is a leading cause of pain and retirement in athletic horses. Hydro-expansive functionalized nanogels, acting as Drug Delivery Systems, constitute one of the current therapeutic prospects. These nanogels have the potential to combine mechanical benefits through polymers with the biological effect of prolonged release of bioactive molecules. The purpose of this double-blinded randomized tolerance study versus negative control was to evaluate the response of healthy joints to a single injection of the expected efficient dose (further referred to as the trial dose) and overdose of nanogels composed of chitosan and hyaluronic acid and featuring a type A endothelin receptor antagonist and a type B1 bradykinin receptor antagonist. The metacarpophalangeal joints of 8 healthy horses were randomly injected with 2.4 mL of functionalized nanogels and 2.4 mL of saline as control on the contralateral limb. Injections were repeated twice at one-week intervals, followed by injection of a triple dose of nanogel on week four. Clinical, ultrasonographic and synovial fluid cellular and biochemical follow-ups were performed up to three months following the first injection. Results: No change in general clinical parameters, lameness or sensitivity to passive flexion of the fetlocks was noted. Mild to moderate synovitis was noted on the day following injection in the treated group, with a significant difference (p < 0.05) compared to the control group. It spontaneously resolved on day 3 following the injections and did not increase with repeated injections. Similar effects were noted after injection of the triple dose but lasted for a week. Synovial fluid markers of inflammation also showed a transient significant increase in the treated group one week after each injection, but no differences were detected at the end of the study. Conclusions: Injections of the expected therapeutic dose of functionalized nanogel in healthy joints induced a mild transient inflammatory response in the joint. Three injections of the trial dose at one-week intervals and injection of thrice the trial dose induce a mildly greater inflammation without harmful effects on joints. Functionalized nanogels are well tolerated prospects for the treatment of osteoarthritis in horses. Their beneficial effects on arthritic joints have yet to be evaluated to determine their therapeutic potential.
© 2024. The Author(s).
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Publication Date: 2024-12-04 PubMed ID: 39633332PubMed Central: PMC11616385DOI: 10.1186/s12917-024-04352-wGoogle Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research presents a double-blinded study on the tolerance of a nanogel created from chitosan and hyaluronic acid, that comes equipped with a type A endothelin receptor antagonist and a type B1 bradykinin receptor antagonist, as a potential treatment for osteoarthritis in horses. The study found that the nanogel induced a mild, short-lived inflammatory response that caused no harm to the joints.

Study Details

  • The study was focused on testing the tolerance of using biologically enhanced Nanogel to treat osteoarthritis in horses. This Nanogel acts as a Drug Delivery System, predicted to combine the benefits of polymers with the prolonged release of bioactive molecules that can help in the treatment.
  • The double-blinded randomized tolerance study administered a trial dose and an overdose of this nanogel to horses by injecting it into their joints. For the trial dose, each horse was injected with 2.4 mL of the nanogel, and for the overdose, it was a triple dose.

Methodology

  • Eight healthy horses were part of the study. One of their joints was injected with the Nanogel, and the opposite joint was injected with saline as a control.
  • The injections were repeated twice in weekly intervals. The triple dose was injected at the end of four weeks.
  • The health of each joint was evaluated clinically, using ultrasonography, and by analyzing synovial fluid. These checks were conducted for three months post the initial injection.

Results

  • No change was noted in general clinical parameters, lameness or sensitivity to passive flexion of the fetlocks in the horses.
  • Mild to moderate synovitis was observed the day after injection in the treated group.
  • Synovial fluid markers indicated a brief increase in inflammation in the treated group one week after each injection.
  • No ill-effects were noted from the triple dose.

Conclusions

  • The therapeutic dose of the nanogel caused a mild, transient inflammatory response in the healthy joints of the horses. This inflammation was slightly greater with thrice the trial dose, but no harmful effects were noted.
  • The findings of the study indicate that these functionalized nanogels are well tolerated prospects for the treating osteoarthritis in horses. However, their beneficial effects on arthritic joints need further study.

Cite This Article

APA
Terlinden A, Jacquet S, Manivong S, Cullier A, Cassé F, Legendre F, Garcia AA, Roullin G, Moldovan F, Sirois P, Banquy X, Galéra P, Audigié F, Demoor M, Bertoni L. (2024). 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. BMC Vet Res, 20(1), 547. https://doi.org/10.1186/s12917-024-04352-w

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 20
Issue: 1
Pages: 547

Researcher Affiliations

Terlinden, Antoinette
  • CIRALE, USC 957, BPLC, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
Jacquet, Sandrine
  • CIRALE, USC 957, BPLC, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
Manivong, Seng
  • Research Center Azrieli, CHU Sainte Justine, Montréal, QC, H3T 1C5, Canada.
  • Faculty of Dentistry, Université de Montréal, Montréal, QC, H3T 1J4, Canada.
  • Faculty of Pharmacy, Université de Montréal, Montréal, QC, H3T 1J4, Canada.
Cullier, Aurélie
  • Université de Caen Normandie, BIOTARGEN UR 7450, Normandie Univ, 14000, Caen, France.
Cassé, Frédéric
  • Université de Caen Normandie, BIOTARGEN UR 7450, Normandie Univ, 14000, Caen, France.
Legendre, Florence
  • Université de Caen Normandie, BIOTARGEN UR 7450, Normandie Univ, 14000, Caen, France.
Garcia, Araceli Ac
  • Faculty of Pharmacy, Université de Montréal, Montréal, QC, H3T 1J4, Canada.
  • TransMedTech Institute (NanoBio Technology Platform), Montréal, QC, H3T 1J4, Canada.
Roullin, Gaëlle
  • Faculty of Pharmacy, Université de Montréal, Montréal, QC, H3T 1J4, Canada.
Moldovan, Florina
  • Research Center Azrieli, CHU Sainte Justine, Montréal, QC, H3T 1C5, Canada.
  • Faculty of Dentistry, Université de Montréal, Montréal, QC, H3T 1J4, Canada.
Sirois, Pierre
  • Department of Microbiology and Immunology, Faculty of Medicine, Université Laval, Q City, QC, G1V 4G2, Canada.
Banquy, Xavier
  • Faculty of Pharmacy, Université de Montréal, Montréal, QC, H3T 1J4, Canada.
Galéra, Philippe
  • Université de Caen Normandie, BIOTARGEN UR 7450, Normandie Univ, 14000, Caen, France.
Audigié, Fabrice
  • CIRALE, USC 957, BPLC, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
Demoor, Magali
  • Université de Caen Normandie, BIOTARGEN UR 7450, Normandie Univ, 14000, Caen, France. magali.demoor@unicaen.fr.
Bertoni, Lélia
  • CIRALE, USC 957, BPLC, Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France.

MeSH Terms

  • Animals
  • Injections, Intra-Articular / veterinary
  • Horses
  • Osteoarthritis / veterinary
  • Osteoarthritis / drug therapy
  • Horse Diseases / drug therapy
  • Chitosan / administration & dosage
  • Double-Blind Method
  • Female
  • Male
  • Nanogels
  • Hyaluronic Acid / administration & dosage
  • Endothelin-1 / administration & dosage

Conflict of Interest Statement

Declarations. Ethics approval and consent to participate: The study protocol was approved by the ComEth Anses/ENVA/UPEC (protocol code 21–037#30112 OA-ACTIVE). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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