Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept

Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder associated with pulmonary emphysema and bronchiectasis. Its management currently consists of weekly infusions of plasma-purified human AAT, which poses several issues regarding plasma supplies, possible pathogen transmission, purification costs, and parenteral administration. Here, we investigated an alternative administration strategy for augmentation therapy by combining recombinant expression of AAT in bacteria and the production of a respirable powder by spray drying. The same formulation approach was then applied to plasma-derived AAT for comparison. Purified, active, and endotoxin-free recombinant AAT was produced at high yields and formulated using L-leucine and mannitol as excipients after identifying compromise conditions for protein activity and good aerodynamic performances. An oxygen-free atmosphere, both during formulation and powder storage, slowed down methionine-specific oxidation and AAT inactivation. This work is the first peer-reviewed report of AAT formulated as a dry powder, which could represent an alternative to current treatments.

Automated summary

This study investigates an alternative administration strategy for augmentation therapy of alpha-1 antitrypsin (AAT) deficiency. The researchers utilized recombinant expression of AAT in bacteria and spray drying to produce a respirable powder. The study successfully formulated active and endotoxin-free recombinant AAT and suggests that the dry powder form could be a potential alternative to current treatments.