Particle engineering for inhalation formulation and delivery of biotherapeutics

Introduction Inhalation as a drug delivery route has been in clinical practice for more than 50 years, with small molecules for the treatment of asthma/COPD capturing the ma jority market share of inhalation products. Since that time, protein therapeutics or biotherapeutics have emerged as a significant class of drugs in clinical development and on the market. Delivery of biotherapeutics directly to the lung via inhalation may hold several ad vantages over subcutaneous and intravenous drug delivery for both systemic and respiratory drug targets. For systemic therapeutics, like insulin, expansive alveolar surface area provides enhanced drug adsorption directly into the blood stream. For respiratory targets, inhalation offers direct drug delivery to the site of disease, potentially reducing the overall required dose and decreasing systemic exposure to the drug and formulation excipients. Development of inhalation formulations with biotherapeutics has nevertheless lagged behind other delivery routes in terms of the number of marketed products. Currently, nebulized recombinant human DNase (Pul mozyme, Genentech) for the treatment of cystic fibrosis is the only marketed oral inhalation biotherapeutic. The small number of currentlymarketed inhaled biologics could partially be attributed to fewer respiratory targets being identified and pursued, but may also be related to the formulation and delivery challenges associated with maintaining protein and inhalation drug product stability.