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

Autor: Janne Raula, Ville Vartiainen, Nurcin Ugur, Luis M. Bimbo, Jenni Viinamäki, Marjukka Myllärniemi, Katri Koli, Esko I. Kauppinen, Eva Sutinen, Janne T. Backman, Emmi I. Joensuu
Přispěvatelé: 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
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
Pulmonary Fibrosis
Pharmaceutical Science
02 engineering and technology
Pharmacology
030226 pharmacology & pharmacy
GAS-PHASE
Idiopathic pulmonary fibrosis
0302 clinical medicine
Pulmonary fibrosis
AQUEOUS-SOLUTIONS
Lung
Aerosolization
Inhalation
Chemistry
PROLIFERATION
Dry Powder Inhalers
021001 nanoscience & nanotechnology
Silicon Dioxide
3. Good health
medicine.anatomical_structure
317 Pharmacy
Systemic administration
Powders
0210 nano-technology
medicine.drug
Antifibrotics
IN-VITRO CHARACTERIZATION
Tilorone
RS
Cell Line
03 medical and health sciences
DELIVERY
L-LEUCINE
In vivo
Leucine
Administration
Inhalation
medicine
Animals
Humans
SALBUTAMOL SULFATE
ta114
WORLD EXPERIENCES PIRFENIDONE
N-ACETYLCYSTEINE
medicine.disease
Mice
Inbred C57BL
MODEL
Dry powder inhaler
3121 General medicine
internal medicine and other clinical medicine
Microscopy
Electron
Scanning
Nanoparticles
Zdroj: INTERNATIONAL JOURNAL OF PHARMACEUTICS. 544(1):121-128
ISSN: 0378-5173
Popis: 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.
Databáze: OpenAIRE
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