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

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.

Informations de copyright

Copyright © 2022. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest R.F., Y.O., A.F., and J.S. are co-founders and shareholders of Neshima Medical Ltd.; D.W. is a consultant to Neshima Medical Ltd.; S.D., M.V., and N.K. declare no competing interests. The use of liquid foams for pulmonary drug delivery has been patented (U.S. Patent number US 2019/0274951 A1).