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Effects of fluorosurfactant structure and concentration on drug availability and biocompatibility in water-in-perfluorocarbon emulsions for pulmonary drug delivery

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Abstract

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.

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Funding

This work was supported by the National Institutes of Health grant number R03AI096029.

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Author notes

  1. Ryan A. Orizondo

    Present address: McGowan Institute for Regenerative Medicine, University of Pittsburgh, 3025 East Carson St, Pittsburgh, PA, 15203, USA

Authors and Affiliations

  1. Department of Biomedical Engineering, University of Michigan, 1101 Beal Ave, Ann Arbor, MI, 48109, USA

    Ryan A. Orizondo

  2. Department of Biomedical Engineering, Carnegie Mellon University, 500 Forbes Ave, Pittsburgh, PA, 15213, USA

    Diane L. Nelson & Keith E. Cook

  3. Department of Radiology, University of Michigan, 1301 Catherine St, Ann Arbor, MI, 48109, USA

    Mario L. Fabiilli

Authors
  1. Ryan A. Orizondo
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  2. Diane L. Nelson
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Correspondence to Ryan A. Orizondo.

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Orizondo, R.A., Nelson, D.L., Fabiilli, M.L. et al. Effects of fluorosurfactant structure and concentration on drug availability and biocompatibility in water-in-perfluorocarbon emulsions for pulmonary drug delivery. Colloid Polym Sci 295, 2413–2422 (2017). https://doi.org/10.1007/s00396-017-4216-4

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  • DOI: https://doi.org/10.1007/s00396-017-4216-4

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