Delivery of biotherapeutics by inhalation aerosol.

The role of inhalation therapy is adapting to changes brought on by advances in several related disciplines. These range from device technology to the molecular and cell biology of the lungs. Acceptable bioavailability and efficacy have been achieved via the oral route for most traditional pharmaceuticals. Unfortunately, injection is the normal mode of delivery with biotherapeutic agents and alternative delivery approaches are needed. Many preclinical and clinical studies with inhaled proteins, peptides, and DNA have been completed and demonstrate that efficacy can be achieved within the lungs and systemically. Despite the promising results, the development of inhaled biotherapeutics is beset with unique problems that require an integrated and rational approach to development. Aqueous protein formulations are often not stable to aerosolization, while stability of powder formulations can be difficult to evaluate in the solid state. Inhaler efficiency and reproducibility are unacceptable with existing devices and, although improvements in technology have brightened the outlook, new devices are not yet available and remain untried with most biotherapeutics. Once delivered to the lungs, these molecules are also subjected to a variety of efficient clearance mechanisms that can significantly reduce the probability of them being effective. Despite these problems, the number of potential drugs being tested via inhalation continues to increase, suggesting some promise of future success. This review discusses the above issues and highlights a variety of biotherapeutics that have been administered as inhalation aerosols.