Bosentan Delivery via Nano Metal-Organic Framework nanoMIL-89 Restores Vascular Homeostasis in Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a progressive vascular disorder characterized by endothelial dysfunction, smooth muscle proliferation, and inflammation. Current treatments, such as Bosentan (an endothelin receptor antagonist), are limited by systemic toxicity and a short half-life. This study aimed to evaluate a nanomedicine formulation of Bosentan using the iron-based metal–organic framework MIL-89 (nanoMIL-89) as a targeted drug delivery platform. Methods: Bosentan-loaded nanoMIL-89 (Bosentan@nanoMIL-89) was synthesized and characterized using microscopy, XRD, FTIR, and HPLC. In vitro assays were conducted on human umbilical vein endothelial cells (HUVECs) and human pulmonary artery smooth muscle cells (HPASMCs) under both basal and lipopolysaccharide (LPS)-induced inflammatory conditions. Results: Bosentan@nanoMIL-89 exhibited no significant cytotoxic or genotoxic effects while maintaining cellular viability. Under basal conditions, it reduced CXCL8 expression by up to 64.38% in HUVECs and 43.34% in HPASMCs. In lipopolysaccharide (LPS)-induced inflammatory conditions, CXCL8 suppression was further enhanced to 94.20% in HUVECs and 58.14% in HPASMCs. In HUVECs, Bosentan@nanoMIL-89 also decreased endothelin-1 (ET-1) release by up to 96.68% and reduced reactive oxygen species (ROS) levels by 46.17% under non-inflammatory conditions. These dose-dependent effects underscore its potent anti-inflammatory and antioxidant properties. Furthermore, Bosentan@nanoMIL-89 promoted angiogenic activity in HUVECs, suggesting therapeutic potential for vascular repair. Conclusion: These findings highlight Bosentan@nanoMIL-89 as a promising nanotherapeutic platform for PAH. By improving efficacy while mitigating systemic side effects, this approach reinforces the broader potential of MOF-based drug delivery systems in the management of vascular diseases.