The efficacy of inhaled antibiotics is often impaired by insufficient drug penetration into plugged and poorly ventilated airways. Liquid ventilation with perfluorocarbon (PFC) containing emulsified aqueous antibiotics, or antibacterial perfluorocarbon ventilation, could potentially improve treatment of respiratory infections when used as an adjunct therapy to inhaled antibiotics. The molecular structure and concentration of the fluorosurfactant used to stabilize such water-in-PFC emulsions will have significant effects on the efficacy and safety of the resulting treatment. In the present study, emulsions are formulated with tobramycin in the aqueous phase using two different fluorosurfactants (termed FSL−PEG+FSL and FSH-PEG) at varying concentrations (C fs ). An aqueous gel is used to evaluate the availability of emulsified drug to diffuse into an aqueous interface (such as mucus or biofilm) for varying emulsion formulations. Lastly, the cytotoxicity of the fluorosurfactants is characterized using human alveolar basal epithelial cells. Results showed that tobramycin delivery is reduced at low C fs due to inadequate drug emulsification and at large C fs due to hindered drug availability. Thus, maximal delivery occurs at intermediate values of C fs equal to 2 and 10 mg mL −1 for the FSH-PEG and FSL−PEG+FSL fluorosurfactants, respectively. The optimal emulsion formulation utilized FSH-PEG and demonstrated improved drug delivery relative to previously used formulations while exhibiting no cytotoxic effect. This work increases understanding of the physical means of pulmonary drug delivery via a water-in-PFC emulsion and represents a critical step in optimizing emulsion formulation for safe and effective treatment.

is a Presidential Postdoctoral Fellow and a Burroughs Welcome Fund Postdoctoral Fellow in Chemical Engineering who is committed to exploring the unique properties of fluorinated materials and harnessing those properties to improve drug delivery vehicles to the lung. She has spent the last six years creating and testing her delivery system on various lung diseases and is currently defining the process of droplet coalescence with the lung lining for drug delivery. As a previous biomedical engineer turned chemical engineer, Diane has developed a unique perspective when it comes to utilizing a broad set of tools in both her research and classroom. She aspires to share her enthusiasm for biology, mathematics, and engineering through teaching and mentoring in the next stage of her career as faculty.

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.

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