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

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http://hdl.handle.net/10138/300847

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Vartiainen , V , Raula , J , Bimbo , L M , Viinamäki , J , Backman , J T , Ugur , N , Kauppinen , E , Sutinen , E , Joensuu , E , Koli , K & Myllärniemi , M 2018 , ' Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice ' , International Journal of Pharmaceutics , vol. 544 , no. 1 , pp. 121-128 . https://doi.org/10.1016/j.ijpharm.2018.04.019

Title: Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice
Author: Vartiainen, Ville; Raula, Janne; Bimbo, Luis M.; Viinamäki, Jenni; Backman, Janne T.; Ugur, Nurcin; Kauppinen, Esko; Sutinen, Eva; Joensuu, Emmi; Koli, Katri; Myllärniemi, Marjukka
Contributor organization: Research Programs Unit
Clinicum
University of Helsinki
Keuhkosairauksien yksikkö
Department of Medicine
Translational Cancer Biology (TCB) Research Programme
Faculty of Pharmacy
Medicum
Department of Clinical Pharmacology
Janne Backman / Principal Investigator
Katri Koli / Principal Investigator
HUS Heart and Lung Center
HUSLAB
Date: 2018-06-10
Language: eng
Number of pages: 8
Belongs to series: International Journal of Pharmaceutics
ISSN: 0378-5173
DOI: https://doi.org/10.1016/j.ijpharm.2018.04.019
URI: http://hdl.handle.net/10138/300847
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.
Subject: 317 Pharmacy
3121 General medicine, internal medicine and other clinical medicine
Idiopathic pulmonary fibrosis
Antifibrotics
Tilorone
Dry powder inhaler
AQUEOUS-SOLUTIONS
N-ACETYLCYSTEINE
PROLIFERATION
MODEL
DELIVERY
L-LEUCINE
IN-VITRO CHARACTERIZATION
SALBUTAMOL SULFATE
GAS-PHASE
WORLD EXPERIENCES PIRFENIDONE
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion


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