Effect of a Surfactant Additive on Drug Transport and Distribution Uniformity After Aerosol Delivery to Ex Vivo Lungs.
Effect of a Surfactant Additive on Drug Transport and Distribution Uniformity After Aerosol Delivery to Ex Vivo Lungs.
复制标题
表面活性剂添加剂对气雾剂输送至离体肺部后药物转运和分布均匀性的影响。
DOI：
10.1089/jamp.2021.0006
复制
发表时间：
2022
影响因子：
3.4
通讯作者：
Corcoran,TimothyE
中科院分区：
文献类型：
--
作者：
Hages,NicholasD;Sembrat,JohnC;Weber,Lawrence;Johnston,DarraghJ;Stetten,AmyZ;Sauleda,Madeline;Mulhern,Brian;Tilton,RobertD;Garoff,Stephen;Rojas,Mauricio;Corcoran,TimothyE
背景：吸入给药可能受到不均匀剂量分布的限制。在气雾剂沉积后将药物分散在肺的内表面上的添加剂可以改善给药均匀性并增加治疗面积。我们之前的研究表明，表面活性剂添加剂可以产生表面张力驱动（Marangoni）流动，有效地将气溶胶递送的药物分散在粘液表面上。在这里，我们试图确定是否添加表面活性剂将增加肺区域之间的气溶胶的运输，也提高剂量均匀性在human lungs.Methods：我们比较了沉积和沉积后分散的表面活性剂（10毫克/毫升二棕榈酰磷脂酰胆碱; DPPC）和盐水为基础的液体气溶胶，混合锝99米（Tc 99米）二亚乙基三胺五乙酸，使用γ射线衍射。在八对通气的人肺中获得了沉积图像。气管插管，交替夹闭主支气管，将生理盐水输送至一个肺，然后将DPPC输送至另一个肺（两侧交替）。在分娩过程中，肺部连续成像15分钟。我们评估运输的沉积气溶胶定量的百分比Tc 99 m在每个肺象限随时间的推移。我们通过测量变异系数（CV =像素相关放射性计数的标准偏差/每个象限内计数的平均值）来量化每个肺象限内的剂量均匀性。结果：随着时间的推移，每个象限中Tc 99 m的百分比没有变化，表明加入表面活性剂后转运没有改善。表面活性剂的加入与CV在较低的内肺象限在每个三个时间点的统计学显着下降，表明在剂量的uniform.Conclusion改善：这些初步结果表明，可能的效用添加表面活性剂的气溶胶，以提高药物分布均匀性，较低的内肺区域。
Background:Inhaled drug delivery can be limited by heterogeneous dose distribution. An additive that would disperse drug over the internal surfaces of the lung after aerosol deposition could improve dosing uniformity and increase the treated area. Our previous studies demonstrated that surfactant additives can produce surface tension-driven (Marangoni) flows that effectively dispersed aerosol-delivered drugs over mucus surfaces. Here we sought to determine whether the addition of a surfactant would increase transport of an aerosol between lung regions and also improve dosing uniformity in human lungs.Methods:We compared the deposition and postdeposition dispersion of surfactant (10 mg/mL dipalmitoylphosphatidylcholine; DPPC) and saline-based liquid aerosols, admixed with Technetium 99m (Tc99m) diethylenetriaminepentaacetic acid, using gamma scintigraphy. Deposition images were obtainedex vivoin eight pairs of ventilated human lungs. The trachea was intubated and the mainstem bronchi were alternately clamped so that saline was delivered to one lung and then DPPC to the other (sides alternated). The lungs were continually imaged for 15 minutes during delivery. We assessed transport of the deposited aerosol by quantifying the percentage of Tc99m in each of four lung quadrants over time. We quantified dose uniformity within each lung quadrant by measuring the coefficient of variation (CV = standard deviation of the pixel associated radioactive counts/mean of the counts within each quadrant).Results:There was no change in the percentage of Tc99m in each quadrant over time, indicating no improvement in transport with the addition of the surfactant. The addition of surfactant was associated with a statistically significant decrease in CV in the lower inner lung quadrant at each of the three time points, indicating an improvement in dosing uniformity.Conclusion:These preliminary results indicate the possible utility of adding surfactant to aerosols to improve drug distribution uniformity to lower inner lung regions.