Aerosolized administration of biopharmaceuticals to the airways is
a promising route for nasal and pulmonary drug delivery, but − in contrast to small molecules − little is known about the effects of aerosolization on safety and efficacy of biopharmaceuticals.
Proteins are sensitive against aerosolization-associated shear stress. Tailored formulations can shield proteins and enhance permeation, but formulation development requires extensive screening
approaches. Thus, the aim of this study was to develop a cell-based in vitrotechnology platform that includes
screening of protein quality after aerosolization and transepithelial permeation. For efficient screening, a previously published aerosolization-surrogate assay was used in a design of experiments
approach to screen suitable formulations for an IgG and an antigen-binding fragment (Fab) as exemplary biopharmaceuticals. Efficient, dose-controlled aerosol-cell delivery was performed with the
ALICE-CLOUD system containing RPMI 2650 epithelial cells at the air-liquid interface. We could demonstrate that our technology platform allows for rapid and efficient screening of formulations
consisting of different excipients (here: arginine, cyclodextrin, polysorbate, sorbitol, and trehalose) to minimize aerosolization-induced protein aggregation and maximize permeation through
an in vitro epithelial cell barrier. Formulations reduced aggregation of native Fab and IgG relative to
vehicle up to 50% and enhanced transepithelial permeation rate up to 2.8-fold.
