Effects of Fluorosurfactant Structure and Concentration on Drug Availability and Biocompatibility in Water-in-Perfluorocarbon Emulsions for Pulmonary Drug Delivery

摘要

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 (Cfs). 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 Cfs due to inadequate drug emulsification and at large Cfs due to hindered drug availability. Thus, maximal delivery occurs at intermediate values of Cfs 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.