Production of L-Leucine Nanoparticles under Various Conditions Using an Aerosol Flow Reactor Method

We have studied the formation of L-leucine nanoparticles under various conditions using an aerosol flow reactor method. Temperatures and L-leucine concentrations for the experiments were selected to vary the saturation conditions for L-leucine in the reactor. In the two extreme cases, L-leucine is either in (i) the condensed phase (110 ∘C) or completely in (ii) the vapour phase (200 ∘C) for all concentrations; (iii) at the intermediate temperature (150 ∘C), the extent of evaporation of L-leucine depends notably on the concentration, and thus partial evaporation and production of residual particles are expected. The size distribution of particles and the particle morphology varied according to formation mechanism with the geometric mean diameter of the particles between 30 nm and 210 nm. Hollow, spherical particles were obtained with the droplet-to-particle method without vaporisation of L-leucine; whereas leafy-looking particles were produced by homogeneous nucleation of supersaturated L-leucine vapour and subsequent growth by heterogeneous vapour deposition.Peer reviewe

Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice

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.Peer reviewe