Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation
Item Type:Journal Article
Citation:Sladek, S., Kearney, C., Crean, D., Brama, P.A.J., Tajber, L., Fawcett, K., Labberte, M.C., Leggett, B. & Brayden, D.J., Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation, Drug Delivery and Translational Research, 8, 5, 2018, 1421 - 1435
SladekRMS.pdf (Accepted for publication (author's copy) - Peer Reviewed) 921.4Kb
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.
Science Foundation Ireland (SFI)
Author: Tajber, Lidia; Sladek, Svenja; Kearney, Clodagh; Crean, Daniel; Brama, Pieter A.J.; Fawcett, Karolina; Labberte, Margot C.; Leggett, Bernadette; Brayden, David J.
Type of material:Journal Article
Series/Report no:Drug Delivery and Translational Research;
Availability:Full text available
Keywords:Salmon calcitonin, Hylauronic acid, Chitosan, Joint inflammation, Synovitis, Nanomedicine, Large animal models
Subject (TCD):Immunology, Inflammation & Infection , Nanoscience & Materials , ANTI-INFLAMMATORY DRUGS , CHITOSAN , HYALURONATE , polyelectrolyte nanoparticles , salmon calcitonin