METAL-ORGANIC FRAMEWORK PREPARATIONS OF BOSENTAN FOR THE FUTURE TREATMENT OF PULMONARY ARTERIAL HYPERTENSION

Abstract

Pulmonary arterial hypertension (PAH) is a rare and progressive Condition with a high death rate among patients. Current treatment options remain limited, and patients face significant challenges, including medications with short half-lives, systemic toxicity, rapid clearance, and drug intolerance. Therefore, there is a critical need for improved drug delivery strategies to address these limitations. This study explores the potential of loading Bosentan, a widely used PAH medication, into porous nanoMIL-89 particles to develop an innovative nano-formulation for PAH treatment. This research systematically evaluates the physicochemical properties, pharmacokinetics, toxicity profile, and therapeutic potential of Bosentan-loaded nanoMIL-89 nanoparticles (BOS@nanoMIL-89). For the first time in Qatar, nanoMIL-89 was successfully synthesized and characterized using multiple analytical techniques. BOS@nanoMIL-89 demonstrated a high drug-loading capacity and sustained drug release profile. In vitro experiments demonstrated the therapeutic potential of BOS@nanoMIL-89 in mitigating the pathogenic processes of PAH. Notably, BOS@nanoMIL-89 exhibited antiproliferative and anti-inflammatory properties, inhibited endothelin-1 (ET-1) release, and reduced oxidative stress, all of which play key roles in PAH pathophysiology. Moreover, its pro-angiogenic properties suggest potential applications in vascular regeneration and repair. In vivo evaluations using zebrafish embryos confirmed the biocompatibility of nanoMIL-89 at low and moderate doses, with no significant impact on viability, hatching rates, or overall development. Organ-specific toxicity assays further revealed the absence of hepatotoxic, neurotoxic, or cardiotoxic effects. In conclusion, BOS@nanoMIL-89 represents a promising strategy for PAH treatment. It offers a sustained-release drug delivery system that enhances therapeutic efficacy while minimizing systemic side effects.