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

Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Ville Vartiainen, Janne Raula, Luis M. Bimbo, Jenni Viinamäki, Janne T. Backman, Nurcin Ugur, Esko Kauppinen, Eva Sutinen, Emmi Joensuu, Katri Koli, Marjukka Myllärniemi 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 h...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research