Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation
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|Title:||Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation||Authors:||Sladek, Svenja
Brama, Pieter A. J.
Labberte, Margot C.
Brayden, David J.
|Permanent link:||http://hdl.handle.net/10197/10032||Date:||26-Jun-2018||Online since:||2019-04-18T08:45:37Z||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.||Funding Details:||European Commission
Science Foundation Ireland
|Type of material:||Journal Article||Publisher:||Springer||Journal:||Drug Delivery and Translational Research||Volume:||8||Issue:||5||Start page:||1421||End page:||1435||Copyright (published version):||2018 Controlled Release Society||Keywords:||Salmon calcitonin; Hyaluronic acid; Chitosan; Joint inflammation; Synovitis; Nanomedicine; Large animal models||DOI:||10.1007/s13346-018-0557-x||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Conway Institute Research Collection|
Veterinary Medicine Research Collection
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