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Drug delivery and translational research2018; 8(5); 1421-1435; doi: 10.1007/s13346-018-0557-x

Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation.

Abstract: Polyelectrolyte nanoparticle constructs (NPs) comprising salmon calcitonin (sCT), chitosan (CS), and hyaluronic acid (HA) were previously established as having anti-inflammatory potential when injected via the intra-articular (i.a.) route to a mouse model. We attempted to translate the formulation to a large animal model, the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation. The aim was to manufacture under aseptic conditions to produce sterile pyrogen-free NPs, to confirm physicochemical characteristics, and to test toxicity and efficacy in a pilot study. NP dispersions were successfully formulated using pharmaceutical-grade source materials and were aseptically manufactured under GMP-simulated conditions in a grade A modular aseptic processing workstation. The NP formulation had no detectable pathogen or endotoxin contamination. NPs were then tested versus a lactated Ringer's solution control following single i.a. injections to the radiocarpal joints of two groups of four horses pre-treated with LPS, followed by arthrocentesis at set intervals over 1 week. There was no evidence of treatment-related toxicity over the period. While there were no differences between clinical read-outs of the NP and the control, two synovial fluid-derived biomarkers associated with cartilage turnover revealed a beneficial effect of NPs. In conclusion, NPs comprising well-known materials were manufactured for an equine i.a.-injectable pilot study and yielded no NP-attributable toxicity. Evidence of NP-associated benefit at the level of secondary endpoints was detected as a result of decreases in synovial fluid inflammatory biomarkers.
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Publication Date: 2018-06-28 PubMed ID: 29947020DOI: 10.1007/s13346-018-0557-xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 explores the development and testing of an anti-inflammatory nanocomplex made up of salmon calcitonin, chitosan, and hyaluronic acid. This was administered through intra-articular injections on an equine model inflamed by lipopolysaccharide. It was found to be non-toxic and potentially beneficial for reducing inflammation.

Research Goals and Methods

  • The primary aim of this research was to translate a previously successful anti-inflammatory nanocomplex, containing salmon calcitonin (sCT), chitosan (CS), and hyaluronic acid (HA), from a mouse model to a large animal model – specifically the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation.
  • An additional goal was to produce these nanoparticle constructs (NPs) under sterile, aseptic conditions to ensure they were free of pathogens and endotoxins. The verification of their physiochemical characteristics was also essential.
  • The final part of their methodology was to test the toxicity and efficacy of these newly created NPs through a pilot study in horses.

Results and Findings

  • The researchers successfully formulated a sterile, aseptic nanocomplex using pharmaceutical-grade materials. This process occurred under Good Manufacturing Practices (GMP) conditions demonstrating its scalability and reproducibility.
  • Once administered via an intra-articular (i.a.) injection to the inflamed joints of the horses, there were no observable signs of toxicity from the nanocomplex over the study period.
  • Physically, clinical observations revealed no difference between horses treated with the NP and those treated with a control solution. However, when examining specific biomarkers associated with cartilage turnover in the synovial fluid, there was a noticeable benefit in the NP-treated animals.
  • This subtle, yet valuable, difference implied that the NP formulation had a positive effect on reducing inflammation at a cellular level. Even though this didn’t translate to apparent physical changes in this initial pilot study, it holds promise for further, in-depth investigations.

Conclusions and Further Implications

  • The researchers conclusively manufactured a nanocomplex for an equine intra-articular injection that showed no attributable toxicity. Beyond that, they found evidence of beneficial effects on secondary endpoints, chiefly decreased inflammatory biomarkers in synovial fluid.
  • This preliminary study forms a solid base for potential, more detailed research into the applications and effectiveness of this nanocomplex in treating joint inflammation in larger animal models or potentially in clinical settings.

Cite This Article

APA
Sladek S, Kearney C, Crean D, Brama PAJ, Tajber L, Fawcett K, Labberte MC, Leggett B, Brayden DJ. (2018). Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation. Drug Deliv Transl Res, 8(5), 1421-1435. https://doi.org/10.1007/s13346-018-0557-x

Publication

Drug delivery and translational research
ISSN: 2190-3948
NlmUniqueID: 101540061
Country: United States
Language: English
Volume: 8
Issue: 5
Pages: 1421-1435

Researcher Affiliations

Sladek, Svenja
  • UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Kearney, Clodagh
  • UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Crean, Daniel
  • UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Brama, Pieter A J
  • UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Tajber, Lidia
  • School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
Fawcett, Karolina
  • UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Labberte, Margot C
  • UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Leggett, Bernadette
  • UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Brayden, David J
  • UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland. david.brayden@ucd.ie.
  • UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland. david.brayden@ucd.ie.
  • Veterinary Science Centre, University College Dublin, Dublin 4, Ireland. david.brayden@ucd.ie.

MeSH Terms

  • Animals
  • Arthrocentesis
  • Biomarkers / metabolism
  • Calcitonin / administration & dosage
  • Calcitonin / pharmacology
  • Chitosan / administration & dosage
  • Chitosan / pharmacology
  • Disease Models, Animal
  • Drug Carriers / chemistry
  • Horses
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / pharmacology
  • Injections, Intra-Articular
  • Lipopolysaccharides / adverse effects
  • Nanoconjugates / chemistry
  • Nanoconjugates / toxicity
  • Pilot Projects
  • Synovial Fluid / metabolism
  • Synovitis / chemically induced
  • Synovitis / drug therapy
  • Synovitis / metabolism

Grant Funding

  • 13/RC/2073 / Science Foundation Ireland
  • 12/RC/2275 / Science Foundation Ireland
  • ISSF Clinical Primer Scheme / Wellcome Trust

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Citations

This article has been cited 10 times.
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