Formulation of High-Performance Dry Powder Aerosols for Pulmonary Protein Delivery

Pulmonary delivery of biologics is of great interest, as it can be used for the local treatment of respiratory diseases or as a route to systemic drug delivery. To reach the full potential of inhaled biologics, a formulation platform capable of producing high performance aerosols without altering protein native structure is required. A formulation strategy using Particle Replication in Non-wetting Templates (PRINT) was developed to produce protein dry powders with precisely engineered particle morphology. Stability of the incorporated proteins was characterized and the aerosol properties of the protein dry powders was evaluated in vitro with an Andersen Cascade Impactor (ACI). Model proteins bovine serum albumin (BSA) and lysozyme were micromolded into 1 mu m cylinders composed of more than 80% protein, by mass. Extensive characterization of the incorporated proteins found no evidence of alteration of native structures. The BSA formulation produced a mass median aerodynamic diameter (MMAD) of 1.77 mu m +/- 0.06 and a geometric standard deviation (GSD) of 1.51 +/- 0.06 while the lysozyme formulation had an MMAD of 1.83 mu m +/- 0.12 and a GSD of 1.44 +/- 0.03. Protein dry powders manufactured with PRINT could enable high-performance delivery of protein therapeutics to the lungs.