Picture of UK Houses of Parliament

Leading national thinking on politics, government & public policy through Open Access research

Strathprints makes available scholarly Open Access content by researchers in the School of Government & Public Policy, based within the Faculty of Humanities & Social Sciences.

Research here is 1st in Scotland for research intensity and spans a wide range of domains. The Department of Politics demonstrates expertise in understanding parties, elections and public opinion, with additional emphases on political economy, institutions and international relations. This international angle is reflected in the European Policies Research Centre (EPRC) which conducts comparative research on public policy. Meanwhile, the Centre for Energy Policy provides independent expertise on energy, working across multidisciplinary groups to shape policy for a low carbon economy.

Explore the Open Access research of the School of Government & Public Policy. Or explore all of Strathclyde's Open Access research...

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

Vartiainen, Ville and Raula, Janne and Bimbo, Luis M. and Viinamäki, Jenni and T. Backman, Janne and Ugur, Nurcin and Kauppinen, Esko and Sutinen, Eva and Joensuu, Emmi and Koli, Katri and Myllärniemi, Marjukka (2018) Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice. International Journal of Pharmaceutics, 544 (1). pp. 121-128. ISSN 0378-5173

[img]
Preview
Text (Vartiainen-etal-IJP-2018-Pulmonary-administration-of-a-dry-powder-formulation-of-the-antifibrotic-drug-tilorone)
Vartiainen_etal_IJP_2018_Pulmonary_administration_of_a_dry_powder_formulation_of_the_antifibrotic_drug_tilorone.pdf
Accepted Author Manuscript
License: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 logo

Download (1MB)| Preview

    Abstract

    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