Systemic delivery of biotherapeutics through the lung: opportunities and challenges for improved lung absorption.

The development of Exubera(®) (inhaled insulin) has paved the way for consideration of future inhaled biotherapeutic products for systemic delivery. This route of drug delivery favors highly potent small peptides without self-association and large proteins resistant to enzymatic degradation for high bioavailability, while likely resulting in transient therapeutic effects. Improved therapeutic benefits with a needle-free delivery, such as inhaled insulin, are also rational pursuits. Molecules and their formulations must be carefully chosen and designed to optimize the rates of lung absorption and nonabsorptive loss. Novel molecular or formulation approaches, for example, Technosphere(®), Fc-/scFv-fusion protein, PEGylation, polymeric or lipid-based micro/nanoparticles and liposomes, offer opportunities to improve lung absorption and therapeutic duration of some biotherapeutics. Critical assessments are now essential as to their therapeutic benefits, safety, patient acceptance and market competition, as carried out for Exubera.