In vitro evaluation of lysophosphatidic acid delivery via reverse perfluorocarbon emulsions to enhance alveolar epithelial repair.

ABSTRACT

BACKGROUND: Alveolar drug delivery is needed to enhance alveolar repair during acute respiratory distress syndrome. However, delivery of inhaled drugs is poor in this setting. Drug delivery via liquid perfluorocarbon emulsions could address this problem through better alveolar penetration and improved spatial distribution. Therefore, this study investigated the efficacy of the delivery of lysophosphatidic acid (LPA) growth factor to cultured alveolar epithelial cells via a perfluorocarbon emulsion. METHODS: Murine alveolar epithelial cells were treated for 2 h with varying concentrations (0-10 µM) of LPA delivered via aqueous solution or PFC emulsion. Cell migration was evaluated 18 h post-treatment using a scratch assay. Barrier function was evaluated 1 h post-treatment using a permeability assay. Proliferation was evaluated 72 h post-treatment using a viability assay. RESULTS: Partially due to emulsion creaming and stability, the effects of LPA were either diminished or completely hindered when delivered via emulsion versus aqueous. Migration increased significantly following treatment with the 10 µM emulsion (p < 10-3), but required twice the concentration to achieve an increase similar to aqueous LPA. Both barrier function and proliferation increased following aqueous treatment, but neither were significantly affected by the emulsion. CONCLUSIONS: The availability and thus the biological effect of LPA is significantly blunted during emulsified delivery in vitro, and this attenuation depends on the specific cellular function examined. Thus, the cellular level effects of drug delivery to the lungs via PFC emulsion are likely to vary based on the drug and the effect it is intended to create.