A Review on Pathogenesis and Advances in Pulmonary Drug Delivery for Chronic Obstructive Pulmonary Disease

Review Article

Abstract

Chronic obstructive pulmonary disease is a persistent, debilitating respiratory disorder characterized by progressive airflow limitation, chronic bronchial inflammation, and parenchymal tissue destruction. Environmental insults, primarily chronic cigarette smoke exposure and airborne particulate matter, trigger an amplified inflammatory cascade governed by alveolar macrophages, neutrophils, and cytotoxic T-lymphocytes. This pathological sequence drives proteolytic tissue breakdown, peripheral airway remodeling, and excessive mucociliary dysfunction. While standard pharmacological regimens rely on bronchodilator and anti-inflammatory regimens to alleviate bronchospasm, conventional systemic interventions remain constrained by poor bioavailability, rapid enzymatic clearance, and systemic adverse reactions. Targeted inhalation therapy directly overcomes these anatomical and physiological limitations by delivering active therapeutic molecules straight to the terminal bronchial tree and alveolar surfaces, circumventing hepatic first-pass metabolism while achieving elevated local drug concentrations. Inhalational drug delivery includes pressurized metered-dose inhalers, dry powder inhalers, and modern soft mist or vibrating mesh nebulizers, each displaying distinct fluid mechanical and dispersion characteristics. Similarly, formulations have evolved to address respiratory clearing mechanisms through engineered micro- and nanocarriers, including large porous microparticles, polymeric nanoparticles, liposomal suspensions, and stimuli-responsive platforms. Incorporating particle aerodynamics and patient-centric device optimization provides a valuable strategy to enhance deep lung deposition, mitigate oropharyngeal impaction, and improve therapeutic compliance across variable disease phenotypes