Fundamental and Targeted Approaches in Pulmonary Arterial Hypertension Treatment.

Abstract

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease marked by vascular remodeling, inflammation, and smooth muscle cell proliferation, with limited treatment options focused primarily on symptom management. The multifactorial nature of PAH, encompassing genetic, autoimmune, and connective tissue contributions, complicates its treatment, while irreversible vascular changes, such as fibrosis, remain unaddressed by current therapies. Fundamental research on molecular pathways and targeted delivery systems has paved the way for advanced therapeutic strategies that aim to modify disease progression rather than merely manage symptoms. Nanoparticle-based drug delivery systems, leveraging controlled release and pulmonary targeting, offer a promising avenue to overcome these challenges. Such systems enable precise localization to pulmonary vasculature, minimize systemic side effects, and support emerging approaches like gene therapy and combination treatments. Future research should focus on refining nanoparticle formulations for personalized medicine, optimizing inhalation delivery systems, and integrating multi-target approaches to achieve curative outcomes in PAH. This review explores pathophysiology of PAH, current pharmacological strategies, and innovative nanoparticle-based therapies, emphasizing their potential to transform PAH treatment and address its underlying mechanisms.