Cardiovascular inhalation for targeted drug delivery in cardiac disease.

Recombinant proteins, cell, and gene therapies are collectively defined as biological drugs or biologics. These therapies have transformed the lives of millions of patients over the past decades, with the number of FDA-approved biologics increasing exponentially in recent years. However, out of approximately 700 biological therapies approved by the FDA in the last 20 years, less than 1% are indicated for cardiac pathologies. The application of biologics in cardiovascular disease has faced significant challenges, including short plasma half-life, the multifactorial complexity of cardiac disease, and the lack of efficient, non-invasive, and patient-friendly drug-delivery routes. This translational gap is particularly pressing given the immense socioeconomic burden of cardiovascular disease, which remains the leading cause of death globally and accounts for billions in annual healthcare costs and lost productivity. Inhalation-based drug delivery has recently emerged as a promising strategy for treating cardiovascular disease, with several proof-of-concept studies demonstrating its potential in heart failure, the most prevalent cardiac condition. This narrative review summarizes the latest experimental evidence in the novel field of Cardiovascular Inhalation, i.e., the lung-to-heart route for biologics. We discuss translational challenges, preclinical evidence, and future perspectives for bringing this innovative approach to clinical practice.