A sustained-release drug-delivery system of synthetic prostacyclin agonist ONO-1301SR: a new reagent to enhance cardiac tissue salvage and/or regeneration in the damaged heart

摘要

Cardiac failure is a major cause of mortality and morbidity worldwide, since the standard treatment for cardiac failure in the clinical practice is chiefly to focus on removal of insults against the heart or minimisation of additional factors to exacerbate cardiac failure, but not on regeneration of the damaged cardiac tissue. A synthetic prostacyclin agonist, ONO-1301, has been developed as a long-acting drug for acute and chronic pathologies related to regional ischaemia, inflammation and/or interstitial fibrosis by pre-clinical studies. In addition, poly-lactic co-glycolic acid-polymerised form of ONO-1301, ONO-1301SR, was generated to achieve a further sustained release of this drug into the targeted region. This unique reagent has been shown to act on fibroblasts, vascular smooth muscle cells and endothelial cells in the tissue via the prostaglandin IP receptor to exert paracrinal release of multiple protective factors, such as hepatocyte growth factor, vascular endothelial growth factor or stromal cell-derived factor-1, into the adjacent damaged tissue, which is salvaged and/or regenerated as a result. Our laboratory developed a new surgical approach to treat acute and chronic cardiac failure using a variety of animal models, in which ONO-1301SR is directly placed over the cardiac surface to maximise the therapeutic effects and minimise the systemic complications. This review summarises basic and pre-clinical information of ONO-1301 and ONO-1301SR as a new reagent to enhance tissue salvage and/or regeneration, with a particular focus on the therapeutic effects on acute and chronic cardiac failure and underlying mechanisms, to explore a potential in launching the clinical study.