Polymer-protein-based dry powder for efficient pulmonary protein delivery

Alejandro Nieto-Orellana, David Coghlan, Malcolm Rothery, Cynthia Bosquillon, Nick Childerhouse, Giuseppe Mantovani, Snow Stolnik
Podium

Pulmonary delivery of protein therapeutics has considerable clinical potential for treating many local and systemic diseases. However, poor protein conformational stability, immunogenicity and protein degradation by proteolytic enzymes are major challenges to overcome. To address these, a family of structurally related copolymers with linear A-B and miktoarm A-B3 macromolecular architectures were non-covalently complexed with the model protein lysozyme to generate well-defined nano-sized assemblies, which were then formulated into dry powders by spray-drying. Trehalose and leucine were used as bulking agent and disperser agent, respectively. The spray-dried powders displayed high protein encapsulation efficiencies (80-100 %) and excellent aerodynamic properties with a fine particle fraction up to 68 %. In aqueous media, the dry powders rapidly released the polymer-protein nanocomplexes. Importantly, these retained their original size upon release from the dry powders. Finally, polymer-protein nanocomplexes provided protection of their protein payloads towards proteolytic degradation. The present study, therefore, shows that our approach could potentially lead to more efficient delivery systems for pulmonary administration of proteins.

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