Hirst Peter H, Pitcairn Gary R, Weers Jeff G, Tarara Thomas E, Clark Andrew R, Dellamary Luis A, Hall Gail, Shorr Jolene, Newman Stephen P
Pharmaceutical Profiles Ltd, Ruddington, Nottingham, United Kingdom.
Pharm Res. 2002 Mar;19(3):258-64. doi: 10.1023/a:1014482615914.
PulmoSphere particles are specifically engineered for delivery by the pulmonary route with a hollow and porous morphology, physical diameters < 5 microm, and low tap densities (circa 0.1 g x 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.
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 99mTc-radiolabeled PulmoSphere particles or micronized particles (Ventolin Evohaler, GlaxoSmithKline, Ltd.) suspended in HFA-134a propellant.
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.
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.
PulmoSphere颗粒经过特殊设计，可通过肺部途径给药，具有中空多孔的形态、物理直径小于5微米且振实密度低（约0.1 g·cm⁻³）。将通过压力定量吸入器（pMDI）递送的PulmoSphere颗粒在人类呼吸道中的沉积情况与传统微粉化药物pMDI制剂的沉积情况进行比较。
9名健康非吸烟受试者（5名男性，4名女性）完成了一项双向交叉γ闪烁扫描研究，评估硫酸沙丁胺醇以99mTc放射性标记的PulmoSphere颗粒或微粉化颗粒（万托林准纳器，葛兰素史克有限公司）悬浮于HFA - 134a推进剂中的肺部和口咽沉积情况。
与准纳器pMDI相比，PulmoSphere制剂的平均（标准差）肺部沉积（呼出剂量百分比）增加了一倍（28.5（11.3）%对14.5（8.1）%，P < 0.01），而口咽沉积减少（42.6（9.0）%对72.0（8.0）%，P < 0.01）。PulmoSphere和准纳器pMDI在肺部均呈现均匀的沉积模式。
这些数据为PulmoSphere技术作为一种改善药物从pMDI靶向递送至下呼吸道的方法提供了体内“概念验证”，并表明PulmoSphere技术也可能适用于递送经肺部吸收的全身作用分子。
