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
Kearney, Clodagh
Crean, Daniel
Brama, Pieter A. J.
Tajber, Lidia
Fawcett, Karolina
Labberte, Margot C.
Leggett, Bernadette
Brayden, David J.
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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 calcitoninHyaluronic acidChitosanJoint inflammationSynovitisNanomedicineLarge 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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