Nebulised heparin as a treatment for lung diseases: formulation challenges and pulmonary drug delivery strategies.

The COVID-19 pandemic further emphasized the global demand for heparin and its expanding clinical relevance, indicating that even one of the oldest drugs in medicine continues to reveal new therapeutic horizons. Traditionally recognized for its anticoagulant and antithrombotic activities, heparin is increasingly being explored for its versatile therapeutic potential in the treatment of a range of pulmonary diseases, including respiratory infections (e.g. COVID-19), Acute Respiratory Distress Syndrome (ARDS), asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. In all of these diseases, inhaled unfractionated heparin (UFH) therapy has been investigated in a number of clinical trials that have demonstrated promise for this drug when administered directly to the lungs. However, using heparin by this "off label" route of administration, poses a number of technical challenges: the physicochemical properties of heparin at therapeutic doses often results in highly viscous formulations, causing device blockage and drug sorption during nebulization. These limitations underscore the need for innovative formulation strategies to improve aerosol flow, reduce dosing inefficiencies, and enable reliable pulmonary administration. Advancing heparin formulations for delivery to the lung could therefore unlock significant benefits for a wide spectrum of respiratory disorders, marking a new chapter in the long medical history of this drug as discussed below.