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

Drug Deliv Transl Res. 2018 Oct;8(5):1421-1435. doi: 10.1007/s13346-018-0557-x.


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.

Keywords: Chitosan; Hyaluronic acid; Joint inflammation; Large animal models; Nanomedicine; Salmon calcitonin; Synovitis.

Publication types

  • Research Support, Non-U.S. Gov't

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


  • Biomarkers
  • Drug Carriers
  • Lipopolysaccharides
  • Nanoconjugates
  • salmon calcitonin
  • Hyaluronic Acid
  • Calcitonin
  • Chitosan