Sharma Ramankur, Khanal Amsul, Corcoran Timothy E, Garoff Stephen, Przybycien Todd M, Tilton Robert D
1 Center for Complex Fluids Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.
2 Department of Chemical Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.
J Aerosol Med Pulm Drug Deliv. 2015 Oct;28(5):394-405. doi: 10.1089/jamp.2014.1167. Epub 2015 Mar 10.
Cystic fibrosis (CF) is associated with the accumulation of dehydrated mucus in the pulmonary airways. This alters ventilation and aerosol deposition patterns in ways that limit drug delivery to peripheral lung regions. We investigated the use of surfactant-based, self-dispersing aerosol carriers that produce surface tension gradients to drive two-dimensional transport of aerosolized medications via Marangoni flows after deposition on the airway surface liquid (ASL). We considered the post-deposition spreading of individual aerosol droplets and two-dimensional expansion of a field of aerosol droplets, when deposited at low fluxes that are representative of aerosol deposition in the small airways.
We used physically entangled aqueous solutions of poly(acrylamide) or porcine gastric mucin as simple ASL mimics that adequately capture the full miscibility but slow penetration of entangled macromolecular chains of the ASL into the deposited drop. Surfactant formulations were prepared with aqueous solutions of nonionic tyloxapol or FS-3100 fluorosurfactant. Fluorescein dye served as a model "drug" tracer and to visualize the extent of post-deposition spreading.
The surfactants not only enhanced post-deposition spreading of individual aerosol droplets due to localized Marangoni stresses, as previously observed with macroscopic drops, but they also produced large-scale Marangoni stresses that caused the deposited aerosol fields to expand into initially unexposed regions of the subphase. We show that the latter is the main mechanism for spreading drug over large distances when aerosol is deposited at low fluxes representative of the small airways. The large scale convective expansion of the aerosol field drives the tracer (drug mimic) over areas that would cover an entire airway generation or more, in peripheral airways, where sub-monolayer droplet deposition is expected during aerosol inhalation.
The results suggest that aerosolized surfactant formulations may provide the means to maximize deposited drug uniformity in and access to small airways.
囊性纤维化（CF）与肺气道中脱水黏液的积聚有关。这会改变通气和气雾剂沉积模式，从而限制药物向肺外周区域的递送。我们研究了基于表面活性剂的自分散气雾剂载体的应用，这些载体在沉积于气道表面液体（ASL）后会产生表面张力梯度，通过马兰戈尼流驱动雾化药物的二维传输。我们考虑了单个气雾剂液滴的沉积后铺展以及在低通量下沉积时气雾剂液滴场的二维扩展，这种低通量代表了小气气道中的气雾剂沉积情况。
我们使用聚丙烯酰胺或猪胃黏蛋白的物理缠结水溶液作为简单的ASL模拟物，它们能够充分体现ASL缠结大分子链的完全互溶性但渗透缓慢的特点，这些大分子链会渗透到沉积液滴中。表面活性剂制剂是用非离子型聚乙氧基乙醇或FS - 3100含氟表面活性剂的水溶液制备的。荧光素染料用作模型“药物”示踪剂，以可视化沉积后铺展的程度。
表面活性剂不仅如先前在宏观液滴中观察到的那样，由于局部马兰戈尼应力增强了单个气雾剂液滴的沉积后铺展，而且它们还产生了大规模的马兰戈尼应力，导致沉积的气雾剂场扩展到亚相最初未暴露的区域。我们表明，当气雾剂以代表小气气道的低通量沉积时，后者是药物远距离扩散的主要机制。气雾剂场的大规模对流扩展将示踪剂（药物模拟物）驱赶到预计在气雾剂吸入期间会发生亚单层液滴沉积的外周气道中覆盖整个气道代或更多区域的区域。
结果表明，雾化表面活性剂制剂可能提供一种手段，以最大限度地提高沉积药物在小气气道中的均匀性并使其能够进入小气气道。
