Dry powder inhalation of hemin to induce heme oxygenase expression in the lung

Zijlstra, G. S., Brandsma, C., Harpe, M. F. H., Van Dam, G. M., Slebos, D. J., Kerstjens, H. A. M., de Boer, A. & Frijlink, H. W., 1-Nov-2007, In : European Journal of Pharmaceutics and Biopharmaceutics. 67, 3, p. 667-675 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)667-675
Number of pages9
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number3
Publication statusPublished - 1-Nov-2007


  • Dry powder inhalation, Fluorescent imaging, Heme oxygenase, Hemin, Mice, Spray drying, heme oxygenase, hemin, rhodamine B, sodium hydroxide, aerosol, animal experiment, animal model, animal tissue, article, controlled study, dispersion, dose response, drug formulation, female, fractionation, histology, mouse, nonhuman, particle size, powder, powder inhaler, protein expression

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