Late Breaking Abstract - New imaging approach to evaluate the in vivo administration of nanostructured mycophenolic acid in a preclinical model of SSC-ILD

<bold>Background:</bold> Interstitial lung disease (ILD) is a serious complication for patients affected by Systemic Sclerosis (SSc) due to pulmonary fibrosis and gas exchange impairment. ILD management include high daily doses of mycophenolate mofetil (MMF). This treatment leads infection, bruising and gastrointestinal bleeding^1,2. <bold>Objective:</bold> To avoid MMF systemic side effects, we developed a nanostructured prodrug of MMF (ADA), and we tested its efficacy in a preclinical model of mild ILD. <bold>Methods:</bold> <fig><object-id>erj;64/suppl_68/PA4297/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> The in vivo protocol is described in fig1. We obtained microCT 3D images that were analyzed with Analyze 14.0 to evaluate lung well aerated and poorly aerated regions³. <bold>Results:</bold> At day 14, BLM mice reported a decrease in the percentage of well aerated area (49%) compared with sham mice (59%) indicating a proper induction of mild ILD. When ADA was administered, no toxic effects were observed in tissue aeration. ADA administration led to a complete reversion of ILD impairment: at t21, indeed, we observed a lung well aerated percentage of 50% for BLM+TAPS while BLM+ADA group recovered to 57% (p<0,05) (fig1). <bold>Conclusions:</bold> This approach highlights that a intratracheal administration of nanostructured MMF prodrug can revert ILD-dependent symptoms. ¹Bergamasco et al. Clinical epidemiology, (2019) ²Pope et al. Nature reviews. Rheumatology, (2023). ³Ravanetti et al. Scientific reports (2021).