Characterization and protective effects of a novel Bosentan nano-particle

Abstract Pulmonary arterial hypertension (PAH) is a life-threatening disorder associated with high morbidity and mortality rates. Bosentan (BST) is a drug commonly used to treat PAH, but its oral preparations still have some shortcomings. A BST nano-particle (FDA@BST) was synthesized and analyzed using transmission electron microscopy, ultraviolet–visible spectroscopy, and cellular uptake. CCK-8, Dihydroethidium (DHE) staining, and flow cytometry were used to detect protective effects of the BST nano-particle (FDA@BST) in pulmonary arterial smooth muscle cells. The FDA@BST was successfully loaded and quickly taken up by cells through endocytosis and released efficiently. The FDA@BST and BST oral drug markedly inhibited H2O2 and hypoxia-induced cell proliferation and oxidative stress, while the bare nano-carrier (FDA) had no significant effects in inhibiting cell proliferation. Moreover, the ability of the FDA@BST limits oxidative stress and proliferation was better than the BST oral drug. However, although BST could almost inhibit hypoxia-induced caspase 3, 8, and 9 activities, the developed FDA@BST was only able to inhibit caspase 3 activity. Altogether, a novel BST nano-particle (FDA@BST) was synthesized, which displayed protective properties in pulmonary arterial smooth muscle cells through its anti-proliferation and anti-oxidative effects.