Overcoming barriers in cystic fibrosis therapy through inhalational lipid nanoparticles: Challenges and advances

Cystic fibrosis (CF) is a genetic disorder that follows an autosomal recessive pattern of inheritance and is characterized by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Cystic fibrosis is implicated in the inflammatory cascades and is recognized as a systemic disease that extends beyond pulmonary involvement, impacting various essential organs and resulting in a plethora of comorbidities. Cystic fibrosis broadly impacts pulmonary airway that is associated with both mortality and morbidity. The condition is attributed to a sequence of critical events, including excessive production of mucus, chronic bacterial infections, respiratory airway obstruction, inflammatory conditions, destruction of the epithelial cells, and ultimately terminal lung diseases. These conditions result in decreased drug performance by creating several barriers like thick mucus lining, biofilm formation, phagocytosis and poor drug disposition, etc. Pulmonary administration is a favourable way of treating respiratory infections, excessive inflammation, and other common manifestations associated with CF lung disease, as it serves as a convenient local delivery path. However, crucial factors that influence the clinical results of inhaled medications include the concentration and duration of the drug's presence in the lungs, as well as its capacity to surmount local extracellular and cellular obstacles. The present review emphasizes the nascent delivery methodologies employed for the localized management of cystic fibrosis. Following a concise overview of the disorder and the regulations governing drug formulation in the context of cystic fibrosis lung barriers, this article outlines present and prospective developments in inhaled lipid nanoparticles and their associated pulmonary toxicities for cystic fibrosis therapy. This paper examines the most promising advanced formulations, emphasizing their benefits and the primary obstacles faced by researchers in this area.