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

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Abstract

Purpose

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.

Methods

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).

Results

Model proteins bovine serum albumin (BSA) and lysozyme were micromolded into 1 μm 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 μm ± 0.06 and a geometric standard deviation (GSD) of 1.51 ± 0.06 while the lysozyme formulation had an MMAD of 1.83 μm ± 0.12 and a GSD of 1.44 ± 0.03.

Conclusion

Protein dry powders manufactured with PRINT could enable high-performance delivery of protein therapeutics to the lungs.

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Abbreviations

ACI:

Andersen cascade impactor

BSA:

Bovine serum albumin

CD:

Circular dichroism

DPI:

Dry powder inhaler

ED:

Emitted dose

ELSD:

Evaporative light scattering detector

FDKP:

Fumaryl diketopiperazine

FPF:

Fine particle fraction

GSD:

Geometric standard deviation

HDODA:

Hexanediol diacrylate

HPMC:

Hydroxypropyl methylcellulose

MDI:

Metered dose inhaler

MMAD:

Mass median aerodynamic diameter

PEG:

Polyethylene glycol

PET:

Poly(ethylene terephthalate)

PPS:

Pre-particle solution

PRINT:

Particle replication in non-wetting templates

PVPVA:

Poly(1-vinylpyrrolidone-co-vinyl acetate)

SD:

Spray drying

SFD:

Spray freeze drying

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Acknowledgments and Disclosures

We thank C. Caudill, T. Rahhal, A. Johnson, J. Perry, J. Coffman, C. Bloomquist, and S. Tian for helpful discussions and technical assistance. We acknowledge Liquidia Technologies for providing PRINT molds. We acknowledge core facilities at UNC, including the Chapel Hill Analytical and Nanofabrication Laboratory (CHANL) which is supported by the National Science Foundation (ECCS-1542015) and the Macromolecular Interactions Facility which is supported by the National Institutes of Health (P30CA016086). This work was funded by the DTRA award (HDTRA1–13–1-0045). J.M.D. is a founder and maintains a financial interest in Liquidia Technologies.

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Authors and Affiliations

  1. Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy, University of North Carolina at Chapel Hill,, Chapel Hill, North Carolina, USA

    Erin M. Wilson, J. Christopher Luft & Joseph M. DeSimone

  2. Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Joseph M. DeSimone

  3. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill,, Chapel Hill, North Carolina, USA

    Joseph M. DeSimone

  4. Department of Chemical and Biomolecular Engineering, North Carolina State University,, Raleigh, North Carolina, USA

    Joseph M. DeSimone

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  1. Erin M. Wilson
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Correspondence to Joseph M. DeSimone.

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Wilson, E.M., Luft, J.C. & DeSimone, J.M. Formulation of High-Performance Dry Powder Aerosols for Pulmonary Protein Delivery. Pharm Res 35, 195 (2018). https://doi.org/10.1007/s11095-018-2452-z

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