The aim of this work was to study the antifibrotic effect of pulmonary administration of tilorone to lung fibrosis. L-leucine coated tilorone particles were prepared and their aerosolization properties were analyzed using two dry powder inhalers (Easyhaler and Twister). In addition, the biological activity and cell monolayer permeation was tested. The antifibrotic effect of tilorone delivered by oropharyngeal aspiration was studied in vivo using a silica-induced model of pulmonary fibrosis in mice in a preventive setting. When delivered from the Easyhaler in an inhalation simulator, the emitted dose and fine particle fraction were independent from the pressure applied and showed dose repeatability. However, with Twister the aerosolization was pressure-dependent indicating poor compatibility between the device and the formulation. The formulation showed more consistent permeation through a differentiated Calu-3 cell monolayer compared to pristine tilorone. Tilorone decreased the histological fibrosis score in vivo in systemic and local administration, but only systemic administration decreased the mRNA expression of type I collagen. The difference was hypothesized to result from 40-fold higher drug concentration in tissue samples in the systemic administration group. These results show that tilorone can be formulated as inhalable dry powder and has potential as an oral and inhalable antifibrotic drug.

Inflammation is the primary problem associated with blood-contacting artificial organs. Leucocytes play an essential role in the generation of the inflammatory response. Inflammation can be defined in a variety of ways. The goal of this research is to develop a biosensor system that is less complicated and faster responding than conventional methods. In this study, highly sensitive QCM crystals were chemically modified to measure changes in adsorbed mass on the surface and were used to detect activated neutrophils. Leucocyte activation was quantified by measuring the change in frequency of the QCM. QCM crystals with immobilized anti-C3a were tested in vitro using different concentrations of neutrophils. The measured frequency shifts were proportional to neutrophil number, indicating that activated neutrophils attach to the surface of the QCM. These results were supported by AFM surface topography measurements and SEM images. This method presents a rapid, inexpensive, and easy bioassay that tests the inflammatory response to blood-contacting artificial organs.