Intra Venous Infusion of Nano-ONO1301 Improve Pulmonary Hypertension in Rat Model

Introduction: We hypothesized that intra venous infusion of newly developed nano-prostacyclin agonist, ONO1301nano, may have some potentials in targeted delivery to damaged lung and improving pulmonary hypertension in rat model. Methods & Results: PAH model rats were induced by the subcutaneous injection with SU5416 (20 g/kg), exposing to chronic hypoxia for 21 days, and normoxia after hypoxia. Treatment group was injected ONO1301nano (3 g/kg) every 7 days cycle after exposure to normoxia for 14 days in normoxia environment. In vivo, the fluorescent images showed that significantly larger number of texas red-labeled nano sized particles were detected in the damaged lung by intravenous administration compared with normal rats (P < .05). Immunostains revelaed that nano particles labeled by texas-red were detected in vimentin positive cells in the lung tissue. On catheterization, the right ventricle pressure/left ventricle pressure was significantly improved in ONO1301nano treatment group compared with the control (P < .01). Histological assessment revealed that the percent medial wall thickness in pulmonary vasculature were significantly ameliorated in treated group (P < .01). In vitro, the expression levels of VEGF and HGF in cultured fibroblasts were increased. Conclusions: Intra venous infusion of ONO1301nano improved pulmonary hemodynamically and histologically in PH model rats with selective delivery to damaged lung, suggesting Nano-prostacyclin agonist delivery system may have potential in new drug for PAH.