Abstract
| Language | English |
|---|---|
| Pages | 121-128 |
| Number of pages | 8 |
| Journal | International Journal of Pharmaceutics |
| Volume | 544 |
| Issue number | 1 |
| Early online date | 12 Apr 2018 |
| DOIs | |
| Publication status | Published - 10 Jun 2018 |
Fingerprint
Keywords
- idiopathic pulmonary fibrosis
- antifibrotics
- tilorone
- dry powder inhaler
Cite this
}
Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice. / Vartiainen, Ville; Raula, Janne; Bimbo, Luis M.; Viinamäki, Jenni ; T. Backman, Janne ; Ugur, Nurcin; Kauppinen, Esko ; Sutinen, Eva; Joensuu, Emmi; Koli, Katri; Myllärniemi, Marjukka .
In: International Journal of Pharmaceutics, Vol. 544, No. 1, 10.06.2018, p. 121-128.Research output: Contribution to journal › Article
TY - JOUR
T1 - Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice
AU - Vartiainen, Ville
AU - Raula, Janne
AU - Bimbo, Luis M.
AU - Viinamäki, Jenni
AU - T. Backman, Janne
AU - Ugur, Nurcin
AU - Kauppinen, Esko
AU - Sutinen, Eva
AU - Joensuu, Emmi
AU - Koli, Katri
AU - Myllärniemi, Marjukka
PY - 2018/6/10
Y1 - 2018/6/10
N2 - 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
AB - 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
KW - idiopathic pulmonary fibrosis
KW - antifibrotics
KW - tilorone
KW - dry powder inhaler
U2 - 10.1016/j.ijpharm.2018.04.019
DO - 10.1016/j.ijpharm.2018.04.019
M3 - Article
VL - 544
SP - 121
EP - 128
JO - International Journal of Pharmaceutics
T2 - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1
ER -