In vivo lung deposition of hollow porous particles from a pressurized metered dose inhaler
In vivo lung deposition of hollow porous particles from a pressurized metered dose inhaler
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DOI：
10.1023/a:1014482615914
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发表时间：
2002-03-01
影响因子：
3.7
通讯作者：
Newman, SP
中科院分区：
文献类型：
--
作者：
Hirst, PH;Pitcairn, GR;Newman, SP
目的。PlmoSphere（TM）颗粒是专门设计用于通过肺部途径输送的，具有中空和多孔形态，物理直径< 5 μ m，低密度（约0.1 g.cm(-3)）。比较了经加压计量吸入器（pMDI）输送的肺球颗粒在人呼吸道中的沉积情况与传统微粉药物pMDI制剂的沉积情况。方法：健康非吸烟受试者9例(男5例；4名女性)完成了一项双向交叉伽玛闪烁成像研究，评估了硫酸沙丁胺醇在肺部和口咽的沉积，硫酸沙丁胺醇被配制成（99m）放射性标记的PulmoSphere颗粒或微颗粒（Ventolin Evohaler(TM)）。葛兰素史克公司（GlaxoSmithKline, Ltd.）暂停在HFA-134a推进剂中。与Evohaler pMDI相比，PulmoSphere制剂的平均（标准偏差）肺沉积（阀外剂量%）增加了一倍(28.5 （11.3)% vs. 14.5(8.1) %）。P < 0.01)，口咽部沉积减少(42.6（9.0)%比72.0 (8.0)%,P < 0.01）。PulmoSphere和Evohaler pmdi均显示肺内均匀的沉积模式。这些数据在体内为PulmoSphere技术提供了“概念证明”，作为一种改善pmdi对下呼吸道药物靶向性的方法。并建议PulmoSphere技术也可能适用于通过肺部吸收的全身性作用分子的输送。
Purpose. PlmoSphere(TM) particles are specifically engineered for delivery by the pulmonary route with a hollow and porous morphology, physical diameters < 5 mum, and low tap densities (circa 0.1 g.cm(-3)). Deposition of PulmoSphere particles in the human respiratory tract delivered by pressurized metered dose inhaler (pMDI) was compared with deposition of a conventional micronized drug pMDI formulation.Methods: Nine healthy nonsmoking subjects (5 male. 4 female) completed a two-way crossover gamma scintigraphic study, assessing the lung and oropharyngeal depositions of albuterol sulfate, formulated as (99m)radiolabeled PulmoSphere particles or micronized particles (Ventolin Evohaler(TM). GlaxoSmithKline, Ltd.) suspended in HFA-134a propellant.Results. Mean (standard deviation) lung deposition, (% ex-valve dose) was doubled for the PulmoSphere formulation compared with Evohaler pMDI (28.5 (11.3) % vs. 14.5 (8.1) %. P < 0.01), whereas oropharyngeal deposition was reduced (42.6 (9.0) % vs. 72.0 (8.0) %, P < 0.01). Both PulmoSphere and Evohaler pMDIs gave uniform deposition patterns within the lungs.Conclusions. These data provided "proof of concept" in vivo for the PulmoSphere technology as a method of improving targeting of drugs to the lower respiratory tract from pMDIs. and suggested that the PulmoSphere technology may also be suitable for the delivery of systemically acting molecules absorbed via the lung.