Zijlstra G S, Brandsma C A, Harpe M F H, Van Dam G M, Slebos D J, Kerstjens H A M, De Boer A H, Frijlink H W
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
Eur J Pharm Biopharm. 2007 Nov;67(3):667-75. doi: 10.1016/j.ejpb.2007.03.021. Epub 2007 Mar 31.
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.
本研究的目的是将氯化血红素制成吸入用粉末,并通过吸入氯化血红素证明小鼠肺部血红素加氧酶1(HO-1)表达的概念验证。氯化血红素由中和的氢氧化钠溶液喷雾干燥制得。该粉末的粒径分布在1至5微米之间。Twincer干粉吸入器的分散显示细颗粒部分(<5微米)为36%。基于Twincer吸入器专门设计的气溶胶箱用于通过吸入氯化血红素诱导小鼠HO-1的概念验证研究。气溶胶箱暴露室内的气溶胶在长达5分钟内保持雾化状态。使用含罗丹明B的气溶胶表明气溶胶箱在整个肺部均有沉积,表明该模型的适用性。此外,吸入氯化血红素显示肺部HO-1蛋白表达呈剂量依赖性增加。总之,氯化血红素成功制成吸入用粉末,且吸入模型可使小鼠肺部HO-1表达得到控制。有必要开展进一步研究以探究吸入氯化血红素在治疗疾病中的效用。