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研究经气管内滴注入离体猪肺内的液体泡沫的肺内分布。

Exploring pulmonary distribution of intratracheally instilled liquid foams in excised porcine lungs.

机构信息

Departments of Biomedical Engineering.

Departments of Neonatology, Carmel Medical Center and the Ruth and Bruce Rappaport Faculty of Medicine.

出版信息

Eur J Pharm Sci. 2023 Feb 1;181:106359. doi: 10.1016/j.ejps.2022.106359. Epub 2022 Dec 13.

Abstract

The applicability of inhalation therapy to some severe pulmonary conditions is often compromised by limited delivery rates (i.e. total dose) and low deposition efficiencies in the respiratory tract, most notably in the deep pulmonary acinar airways. To circumvent such limitations, alternative therapeutic techniques have relied for instance on intratracheal liquid instillations for the delivery of high-dose therapies. Yet, a longstanding mechanistic challenge with such latter methods lies in delivering solutions homogeneously across the whole lungs, despite an inherent tendency of non-uniform spreading driven mainly by gravitational effects. Here, we hypothesize that the pulmonary distribution of instilled liquid solutions can be meaningfully improved by foaming the solution prior to its instillation, owing to the increased volume and the reduced gravitational bias of foams. As a proof-of-concept, we show in excised adult porcine lungs that liquid foams can lead to significant improvement in homogenous pulmonary distributions compared with traditional liquid instillations. Our ex-vivo results suggest that liquid foams can potentially offer an attractive novel pulmonary delivery modality with applications for high-dose regimens of respiratory therapeutics.

摘要

吸入疗法在一些严重的肺部疾病中的应用往往受到有限的输送速率(即总剂量)和呼吸道(尤其是深部肺腺气道)中低沉积效率的限制。为了克服这些限制,替代治疗技术例如依赖于气管内液体滴注来输送高剂量治疗。然而,此类后期方法存在一个长期存在的机械学挑战,即尽管存在主要由重力效应驱动的不均匀扩散的固有趋势,但仍要在整个肺部均匀地输送溶液。在这里,我们假设在注入之前将溶液发泡可以显著改善注入液体溶液的肺部分布,这是由于泡沫增加了体积并降低了重力偏差。作为概念验证,我们在离体的成年猪肺中表明,与传统的液体滴注相比,液体泡沫可以显著改善肺部的均匀分布。我们的离体结果表明,液体泡沫可能为高剂量呼吸治疗方案提供一种有吸引力的新型肺部输送方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9e/9850415/1426162ff96a/ga1.jpg

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