Dry powder inhalation of hemin to induce heme oxygenase expression in the lung.
The purpose of this study was to formulate hemin as a powder for inhalation and to show proof of concept of heme oxygenase 1 (HO-1) expression in the lungs of mice by inhalation of hemin. Hemin was spray dried from a neutralized sodium hydroxide solution. The particle size distribution of the powder was between 1 and 5 microm. Dispersion from the Twincer dry powder inhaler showed a fine particle fraction (<5 microm) of 36%. A specially designed aerosol box based on the Twincer-inhaler was used for a proof of concept study of HO-1 induction by inhalation of hemin in mice. The aerosol in the exposure chamber of the aerosol box remained aerosolized up to 5 min. A rhodamin B containing aerosol was used to show that the aerosol box gave deposition over the entire lung indicating the suitability of the model. Additionally, inhalation of hemin showed a dose dependent increase in HO-1 protein expression in the lungs. In conclusion, hemin was successfully formulated as a powder for inhalation and the inhalation model allowed controlled HO-1 expression in the lungs of mice. Future studies investigating the utility of inhaled hemin in treating disease states are warranted.
Zijlstra
G S
GS
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
Brandsma
C A
CA
Harpe
M F H
MF
Van Dam
G M
GM
Slebos
D J
DJ
Kerstjens
H A M
HA
De Boer
A H
AH
Frijlink
H W
HW
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D015153:Blotting, Western; D002626:Chemistry, Pharmaceutical; D003890:Desiccation; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005456:Fluorescent Dyes; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006427:Hemin / Q000008:administration & dosage* / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008805:Mice, Inbred A; D008855:Microscopy, Electron, Scanning; D011208:Powders; D012235:Rhodamines; D012995:Solubility
D000336:Aerosols; D005456:Fluorescent Dyes; D011208:Powders; D012235:Rhodamines; D006427:Hemin; D051547:Heme Oxygenase-1