Conference 2021 Live Talk


Talk title

Serelaxin-nanoparticles abrogates inflammation and remodeling associated with chronic allergic airways disease through specific myeloid cell subsets


Authors and Affiliations

Amlan Chakraborty1, Anita A. Pinar1, Simon G. Royce1, Cordelia Selomulya2 and Chrishan S. Samuel1

1. Monash Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Victoria, Australia
2. School of Chemical Engineering, University of New South Wales, Sydney, New South Wales, Australia




Chronic allergic airways disease (AAD) is a hallmark T Helper type 2 (TH2) disease characterised by airway inflammation (AI), airway remodeling (AWR) and airway hyperresponsiveness (AHR). Current treatments of AAD mainly focus on targeting AI and its contribution AHR, with the use of corticosteroids. However, there are no therapies for the direct treatment of AWR, that can contribute to AHR independently of AI, and which contributes to corticosteroid resistance. The acute heart failure drug, serelaxin (recombinant human gene-2 relaxin/RLX), has been shown to ameliorate lung fibrosis and related AHR/lung dysfunction in various pre-clinical disease model, but requires continuous systemic delivery or daily intranasal administration.


We developed serelaxin-conjugated biodegradable nanoparticles (NP-RLX) and demonstrated for the first time the use of these particles as translational therapies for the treatment of AAD in a mice model of Ovalbumin (OVA) induced AAD.


Intranasally administered NP-RLX demonstrated uptake specifically by alveolar monocytes/macrophages but not by other inflammatory cells such as neutrophils and eosinophils. The uptake of serelaxin was 33% more in mice induced with airway inflammation than their saline-treated (vehicle) counterparts. However, the particles did not penetrate the nucleus and were non-inflammatory in themselves. Furthermore, when investigated for the specific alveolar macrophage subsets (CD45+ cells) involved, M2 macrophages (F4/80+CD206+) had 3.5 fold higher uptake than M1 macrophages. Another dendritic cell like populations (CD11c+) cells demonstrated that only CD206+ cells were able to take up NP-RLX. Furthermore, another macrophage subset characterised as CD68hi/F4/80+/CD11c+ demonstrated ~8 fold higher uptake of NP-RLX than their CD11c- counterparts.


The results demonstrate for the first time, the retention of serelaxin activity within the inflamed and fibrosed airways/lung and directs that CD206+ macrophages are activated and elevated for mitigating the anti-inflammatory and anti-fibrotic effect of serelaxin observed.