The wet bridge transfer system: a novel tool to assess exogenous surfactant as a vehicle for intrapulmonary drug delivery.

Due to its branching structure, drug delivery to the peripheral areas of the lung is a major challenge. Consequently, most pulmonary therapies utilize large systemic dosing, with the potential for adverse side effects. One proposed strategy to overcome this challenge is to use exogenous surfactant, a material capable of distributing throughout the lung, as a pulmonary drug delivery vehicle. The objective was to develop and test an in vitro system to rapidly assess surfactant based therapies prior to animal studies. The Wet Bridge Transfer System consisted of two connected wells in which drugs were instilled into a delivery well and function was tested in a remote well which mimicked the remote areas of the lung where drug activity would be required. The system was used to assess surfactant as a carrier for antibiotics (Gentamicin, Ciprofloxacin, and Colistin) by measuring their ability to kill Pseudomonas aeruginosa bacteria in the remote well. Anti-inflammatory agents (Budesonide and a host defense peptide, CATH-2) with and without exogenous surfactant were examined using stimulated macrophages in the remote well and IL-6 concentration as an outcome. The results showed that being paired with surfactant, Gentamicin and Ciprofloxacin, but not Colistin, had significantly greater bacterial killing in the remote wells. Similarly, when combined with a surfactant, both Budesonide and CATH-2 significantly lowered IL-6 concentrations. We conclude that the wet-bridge system can be used to rapidly screen surfactant-based therapies prior to their assessment in vivo. Furthermore, exogenous surfactant was an effective delivery vehicle for several antimicrobial and anti-inflammatory therapeutics.